What if you could be the villain? In every Resident Evil game thus far you always get to play as the hero. What if you could instead be the one who releases the virus or steals information?
Of course, canonically speaking I think that any game involving the player as the villain would have to be non canon. I believe this because it would lead to a lot of disappointment in the story line and plus I think it would leave a lot of endings open for the player. Like, for example, depending on how well you played the game (Based on stealth, remaining health, etc.) then you could either complete the task that Wesker failed to complete (complete...global...penetration...xD) or become another William Birkin and maybe even play as the newly mutated monster until you're killed.