I really only played AC3 to see how they chose to represent a Mohawk character. I'm not Mohawk, but Cree from Canada, and other than Prey (which I picked up within the last year or so for the same reason) I'd never had the opportunity to play as a Native character in a game. I actually thought that Connor's mother is a much better character than he was, seeing as how she subverts all of Haytham's/the audience's expectations of what a Native character is supposed to be, whereas Connor is yet another stoic warrior, even if he is more fleshed out than most other incarnations of that kind of character.
Much like Prey, though, Assassin's Creed sets up its science fiction so that the spirituality of the protagonist's nation (Cherokee in Prey, Mohawk in AC3) is premised on ancient contact with aliens. Not only does it imply that indigenous peoples are incapable of developing systems of understanding the world on their own, but that their knowledge was based on a profound misunderstanding of a advanced civilization. Kind of a nitpicky thing, but it bothers me anyway.
There's an encounter with a couple NPCs early on in the game where one explains to the other what an indigenous nation is, and how that differs from commonly held notions of "tribes". It was super bizarre and the guys ended up duking it out, and I think that has got to be the most memorable part of the game for me.