We know that Christopher has had at least much, if not most, of the story of SOTM figured out before he started making it; things are revealed in Rook City which pay off in Shattered Timelines, so it's clear that there is a Plan with a capital P which is playing out through the storyline. What that makes me wonder, then, is about Heroes and Villains who couldn't possibly have been part of the Plan in its original stages, because they were created by fans after the game succeeded, and never would have been if it hadn't.
Case 1: Kismet. Kismet has the power to bend luck to her favor using The Talisman. Was there a luck-controlling villain in the original Plan? If so, what became of the parts of that concept which didn't match Kismet? Was this abandoned villain intended to be Setback's nemesis, or was Setback to the Plan added after Kismet was designed, so that Kismet would have a nemesis?
Case 2: The Scholar. I don't know the full details on the Scholar, so I'm not assuming he is a fan creation, but he was listed on the ST Kickstarter page as something that would only exist if the backers Kicked enough. So there was a possibility he would never have been published, and if that was the case, what would have become of his (currently nonexistent, but presumably coming in a future set) nemesis?
Here's my theory...I think originally the character who would become Setback was a villain, or at least a mook for some villain, and that he was both the proto-Kismet and the nemesis of the Scholar. His appearance on Shock Rounds in Rook City will probably be explained somehow by his mechanics when he's released (I'm guessing he has at least one card that causes him to redirect damage dealt to villain targets to himself, or less probably that causes him to count as a villain target for targeting purposes), but that doesn't mean he wasn't slated to be a villain at the time RC was published. And if he was originally something similar to what Kismet would end up being, it would seem natural for him to have been the nemesis of the Scholar, just as it would make a fair bit of sense if Scholar and Kismet were nemeses - Scholar has an innate ability to sense and manipulate the "threads of existence", and that's really not terribly different from what Kismet does when making her own luck (they even both use artifacts to do it). Had Scholar and Kismet both never existed, "Twitchy" from Shock Rounds would have just been a random mook who we'd never see again; had only Kismet existed, any plans for Scholar's nemesis-to-be might have been merged into her and/or Setback, depending on how villain-specific they were. But had only Scholar existed, I think Setback might have ended up being a Shattered Timelines villain with Scholar's nemesis icon.
Case 3: Miss Information. This is pretty much the same deal as Kismet, so I won't go into it too much more. We have no evidence currently that Parse was ever part of The Plan, so it's entirely possible that she was created simply to fill the need for Miss Info to have a Nemesis. (Personally I think she ought to have the entire Freedom V as nemeses, akin to Iron Legacy, but perhaps this was avoided so as not to step on the toes of the Vengeful Five. It'd be kind of unfair anyway, given that you're only able to damage her on one side, not that this stopped The Chairman or worse yet The Dreamer.) But it's also conceivable that plans for "an archer", "an Aspie hero", and/or "a hero whose power source is Omnitron's Cosmicizer" all existed originally, and it's interesting to speculate on what might have happened if "The Assistant" had remained an elusive Kickstarter award and never actually been published.