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Had the thought: What if Shepard is the Big Bad for Mass Effect 4 and maybe 5 and 6?
It would fit the idea that two of the three endings are the result of indoctrination. It would be a cool twist, but the chance of upsetting players would almost certainly push Bioware away.
My thought is Shepard and Liara's Daughter as a squad mate or even as the main character.
That would mean they’d have to set the game a good 100 years after ME3, but it’s certainly a possibility. The passage of so much time would give them a lot of room to change the state of the setting.