I actually see a lot of potential games that could be made, although I have my favorite 3.
1) MEA2: The Ryders are trying to deal with the fallout of their decisions and the war with the Archon, while continuing to expand and explore. Kett, Angara, and MW people are struggling with rebellion and political upheaval, even as the arrival of new arks, lost colonies, and the further complicate matters, while in the shadows conspiracies continue to maneuver.
2) ME Fall: Shepard defied Catalyst, and now both are gone. Leaderless Reapers turn on each other as the harvest continues. As members of the resistance, you are fighting to save as many lives as possible from the harvest. Possibly episodic, playing alternatively as resistance fighters on Earth, Palavan, and Thessia from day one of invasion, a Hammer member shot down before reaching London, and an Allied Command Operative/leader.
3) ME Rogue's Gallery: A prison ship of the galaxy's worst, including Shepard's prisoners, captured Cerberus, outlaw mercs, gangs, BSS Purgatory survivors, and general scumbags, suffers critical damage leading to a prisoner takeover and an impromptu trip through the Omega 4 relay. After playing a key role in the revolt and determining the fate of the surviving crew you evacuate the failing ship with your chosen prisoner faction. Depending on your faction, choices, and Shepard's choices you can acquire different teammates and alliances with some (not all) of the other factions as you seek to survive the dangers of the wreckage field and gather the resources to suvive and make your way back to reclaim your place in the galaxy at large.
4) MEA Outcast Path: Play as an outcast after the Uprising, fighting for survival and a new home, and picking a side as the Charlatan rises
5) ME4: The Galaxy is struggling to rebuild after the victory at Earth, but without Shepard and the Reapers to unite them old scars are tearing apart the fragile new alliances, and past mistakes come back with a vengeance. Play as a Specter trying to keep the peace, a colonial soldier seeking independence, or a merc out to build a personal empire. Find resources and allies, and tip the delicate balance of the galaxy to save the council worlds or tear them apart.
6) MEA Plymouth: Play as a colonist aboard a failing post-Reaper invasion ark attempting a desperate landfall in an uncharted cluster in Andromeda. Collect Supplies and Survivors, establish bases, and scout the hostile planet as you try to forge a survivable colony against all odds.