Personally, I have to have some particular mods in order to keep the storyline I have going in my save. I did split my mods between two separate files, though, so that not all of them are at play. For instance, the cc that pertains to the 18th century, certainly isn't necessary in a save set somewhere in the 23 century . . .
Both need MCCC, to be sure. But only one of them needs Road to Fame. I do have some smaller mods in play that enable my Rock Star to write songs faster, so there's no having to start from the top completely, when he doesn't get it done in the one sitting. Another small mod allows him to license more than one song within a week. In fact, he could spam if he wanted to. And, yes, I have two copies of my game that I keep separate by adding.Ancestral when I wish to play in the 23rd century. I would imagine having mods.ancestral in the same Sims4 folder would do just as well, but I am too chicken to find out. LOL