There are a number of key elements to the plot that will probably be central to MEA2
1) The Kett War: While the Archon is dead, a good chunk of the Kett fleet is destroyed, and Kett forces largely pushed back or eliminated on Eos, Voeld, Kadara, and possibly Elaaden, the Kett in Helios are a long way from being beaten. We have not found their main base of operations, and there are any number of lost Angara (or other spiecies) colonies that are still under Kett occupation, not to mention other Kett labs, slave camps, and Remnant facilities they may control. The Kett will probably be facing an internal conflict between 3-4 factions: The Archon's remaining loyalists (Cardinal), the die-hard supporters of the Kett empire (Primus or Prefect), and 1-2 commanders trying to seize the cluster as their personal fiefdom, with a possible end goal of taking the Empire (Primus and/or Invictor). The power and willingness to talk of the various factions will depend on how you dealt with Cardinal, Primus, and the Kett bases. You will not be able to prevent the Kett from notifying the Empire of the Initiative's arrival, although if you play your cards right the Milky Way DNA and other such data can be kept from leaving the cluster. It is probable that at the end of the game a large force from the main Empire will hit the cluster, and based on the choices you make you will either be able to use the Scourge to block their entry, use your allied forces to fight a delaying action while you evacuate and set up a new line of defense, or just get run over and lose a lot of people and worlds
2) The Remnant, Jardaan, and Scourge guys: We don't know when the Jardaan and the Scourge guys disappeared or where they went, or why they were fighting. We don't know who were the good guys or the bad guys, or if there really were either, or who was winning, only that someone was getting close to Meridian, so it had to be evacuated. Looking for answers to all of these questions will undoubtedly be an important part of the next game. The fact that the main Remnant vessels docked briefly with Meridian, presumably for a download, and then disappeared into the Scourge bound for parts unknown certainly indicates that they are going to make something, presumably Jadaar or Scourge-guys related, happen that we aren't really ready for. Given the Archon's obsession with the Remnant, it is quite possible that the Jardaan and scourge-guys were localized to Helios and possibly adjacent clusters. If this is the case the remainder of these groups are unlikely to have gone too far, and may return and become actively involved in the situation as well, providing additional groups to negotiate with/fight, especially if, like everyone else, they have become factionalized. It is almost certain that they will return at some point, but whether that is in the next game or further down the road is unknown.
Conspiracy: the Jardaan were original Angarans trying to genetically uplift themselves into a super-race (yes like Khan), and the scourge guys were fighting for Angara as God or Nature intended them. We know that the Angara were being tinkered on, and the Angaran AI and statue on Voeld indicate that the Angara there used to be significantly different, so...
3) Politics, Power, and Primacy: ME:A has been about gaining a foothold in Helios, but it is almost certain that ME:A2 will centrally figure holding, expanding, and controlling that turf. Based on your choices, there will probably be more than a dozen various factions of various power and attitude regarding you and each other, plus almost certainly groups that you have yet to encounter, which will also complicate the mix. Negotiating with Kett factions could save lives, but would almost certainly alienate some of your allies. With Voeld mostly reclaimed for the Angara the Official Angaran Government at the official capitol on Voeld will be trying to reclaim power from the De Facto Angaran government on Aya, while the Moshe and the Resistance, who have no official standing but a lot of power, will be actively trying to influence decisions. The Rokaar may have some sway, as well as some independent Angaran bases such as Paradise. On the Milky Way side, New Tuchanka, Kadara, and Advent are all independent (plus the exile base if you backed it), have unknown objectives that we will want to discover, and are (at least Morda and Sloane), still facing leadership challenges. It will be important to keep these nations from becoming a threat, even as we seek to make allies of them to deal with continuing dangers such as the Kett. The Initiative itself continues to face internal strife as well. The Nexus leadership and the colonies will almost certainly fight over rights and authority, and we will have to decide where the boundaries lie, try to prevent things from turning into another uprising since the kett have been pushed off most of our colony regions, and possibly preventing colonies from declaring independence from the Nexus. Not to mention helping decide if the Initiative's eventual capitol will be at Prodromos, Meridian, or the Nexus and founding yet more colonies for whomever, as well as finding any remaining arks, original 5 or possible follow ups, and seeing if they will join any current group or are going independent too, as the Quarians may be. Of course the make-up and authority of the eventual Nexus Council will have to be decided as well. Will it be the central government of the cluster, an international mutual defense organization like NATO, a permanent forum and negotiating table like the UN, or something else entirely? What are the limits of its powers? Everyone who didn't have the first councilor as one of their group is going to start out pissed and obstructionist, and there is a good chance that someone will try (and possibly succeed) in assassinating said Councelor, which means you will be running around trying to solve the hit and keep your alliance from burning down at the same time. And finally there are the Pathfinders. Who do they work for? IE, will they essentially become Council Spectres, or do they just work for the Initiative, or if Meridian declares independence do I work for them, or does every group get one, or do they work independently on behalf of everyone? Decisions, decisions...
4) Shadow Games: There is almost certainly more than one organization working in the shadows, although we quite probably will not see the motivations, identities, and end goals of the major players, although we may encounter some major reveals, such as proof of the non-death of Alec Ryder or Jien Garson or evidence that the Moshe is involved in a deep game of her own. The most obvious shadow organization is the Benefactor. We will probably be chasing clues about the Benefactor's identity, goals, and operations on the side for much of the game, and will probably uncover more bits of the organization, though nothing to really compromise it. That seems like something for down the road. It is likely you will discover evidence that the Benefactor, or a competitor, stole a large amount of top of the line Initiative equipment, possibly including Pathfinder ships, during the Scourge incident that supposedly killed Jien Garson and hid them away in one or more secret bases. There seems like a strong possibility that Alec & Jien put together contingencies to uncover and neutralize the Benefactor, and these operations are moving forward with or with them. An interesting twist would be if they had both faked their deaths and are now operating independently to carry out their mission, possibly due to a level of paranoia and distrust engendered by the situation. Of course, if Jien is still alive it is probable the Benefactor has her. The Collective may be an offshoot or piece of another organization or it may be totally independent, but whatever the case may be, it is unlikely that Kadara Port is the end goal for the organization. We will probably see their operations moving across the cluster regardless of who owns Kedara, although that situation may influence how we handle Collective ops. Unless we really clamp down on it, it is likely that by the end of the game the Collective will be well on its way to filling the place of the Shadow Broker back in the Milky Way. Given that the actual Shadow Broker changed bosses 2-3 times before the Initiative set out, it is probable there are Shadow Broker operatives in place, possibly planted by multiple Shadow Brokers with different missions to fulfill and no knowledge of the other Shadow Broker groups. There is a decent chance that we will uncover enough information to at least be aware of the existence of some of these operations. Additionally, there is Cerberus. Its mandate is to ensure human dominance, and it is unlikely that they would not work to assure human dominance in Andromeda as well. The Initiative is almost certainly heavily seeded with Cerberus operatives, possibly including TIM's trusted scientist/assistant who was supposed to keep him from going crazy. Whoever they are, they will be running operations that will probably cross our path, although they are unlikely to be "hilariously incompetent." The Kett obviously have their own shadow ops going, based on the information we have on In victor and our interaction with Primus, plus, possibly, Archon subverting the whole expedition to his own ends. Finally, it is possible the Moshe could be playing her own game, probably related to restoring the Angara to their ancient glory or exploring the Remnant.
Conspiracies: The Rokaar work for the Moshe's organization, the Moshe was a voluntary part of the Archon's Remnant mission
5) Exploration, Arks, and Colonies: Exploration and colonization is still going to be important in ME:A2. The Scourge holds many secrets, and we have a war to fight, allies to discover, and colony sites to find. There are undoubtedly lost Angaran colonies to rediscover, although it is unlikely we will find them all this game. Many of them will have their own form of Resistance, and it is possible that we may find a surviving Angaran fleet base which has successfully kept the Kett at bay all this time using some combination of skill and the Scourge. Unfortunately, this will be a series of first contacts, and, since we know that the Angara have Kett collaborators in their ranks, having Jaal along won't necessarily smooth the way, and some of them will undoubtedly go sideways. In addition, the Kett may use captured families or other leverage to force collaborators to sell out Aya, and we will probably face a street fight defending Aya port. It is possible that we will encounter other races as well, which will present its own challenges. Finally, we currently have at least one official ark left to find, plus any other arks built as follow ups or by outside organizations. Cerberus has a policy of getting operatives' families out of harm's way, a vested interest in human dominance in Andromeda, and massive secret ship construction capacity, so it is entirely possible that they built and sent another ark, even if it is a smaller one. Similarly, there is a possibility that the Benefactor arranged for a personal ark rather than with the main Initiative force, and there are others (Aria, Henry Lawson, the Natanus sisters, Shadow Broker, Novaria, etc.) who possess the resources, power, shady connections, and motivation (protecting third clone-daughter genetic legacy, avoiding sororicide) to launch an expedition of some size which will take advantage of the Initiative's ground work. These arks would provide significant challenges and moral dilemmas, but could also provide significant bonuses if you can ally with them or get them to integrate into an existing allied faction. Finally, as part of the arks, we will be able to import a ME3 save, allowing Sheperd's actions in ME1&2, and possibly part of 3, to have an impact on the people and issues that turn up in Andromeda.
Conspiracy: One of the arks has a Yahg onboard that we can gain as a (romanceable?) crewmate
6) Angara: We will be working to find lost Angara families, free work camps and exultation facilities, and find additional Angaran colonies, as well as continuing trying to find a "cure" for exultation, although that is unlikely at this time we will find one. These projects will restore parts of families and help determine the fates of others, but will uncover kett collaborators we will have to deal with, betrayals we will have to help overcome, and raise conflict between the lost colonies and current Angara space, which we will have to manage. If the political fallout becomes too bad we may have to choose sides and assist in removing the competition. The Rokaar will coalesce around a new leader, who will inspire a resurgence in power and continue to target the Milky Way colonists.
7) Family: We will continue to discover information and memories of Alec's, helping us to start piecing together his plan, even as we have to deal with the fallout of his decisions, such as (unsuccessfully) trying to hide the Reaper invasion. We will continue to search for a cure for Mom, and will find at least a short-term one, possibly tied to efforts to cure the supervirus. Twin joins the Tempest and finds a romantic partner, although the two things are not necessarily connected. Twin and partner, Ryder and Partner, or both start the next generation of the Ryder family. There should be one or more entertaining scenes where partner(s) meet Mom. The escalating political situation causes rifts between family members/partners, with Mom acting as mediator/glue, and possibly has various individuals choosing to take up different sides/nationalities and leaving to support them
Conspiracy: At the end of the game a non-dead Alec uses SAM to backdoor into Ryder's mind and deliver an important message, probably regarding the Benefactor
8) Tempest: Gil and Kallo will continue to modify the Tempest, probably finding a way to add at least a limited weapons capability, as well as Remnant mods which can be rendered functional or non-functional at will, to help avoiding being killed by the Scourge. We will have missions to acquire the parts, materials, etc. to support these projects and other ones for Nomad. In addition we will have access to additional paint schemes for both, including Blood Dragon. There will be additional minor cosmetic tweaks we can make to the interior of the Tempest as well as individual, crew, and mission specific collectables that add over the course of the game. Due to political issues, internal conflicts, and request (yours or theirs) some crewmembers may leave to take up duties elsewhere, while at the same time we will have new potential crewmates available to pick up, both ship side and squad.
9) Outposts/Colonies: They will continue to grow, and as planet viability begins to increase they begin to replace hostile presence in the outlands with friendlies, and provide scientists and security for any captured facilities. In addition, all outposts have a security force/HQ with access to strike missions. Finally, outposts have discovered a new set of problems which Ryder is invited to solve
10) Romance: For those not contented with Ryder's current options, there is a new crop of romance options to avail yourself of. In addition, Ryder can also make use of significantly more romance material if continuing a current romance. For non-romanced NPCs there are other fish in the sea, and many NPCs will pair up and potentially start making babies, although due to conflict, tragedy, irreconcilable differences, and Ryder, some of these relationships will not last.