Well, we could avoid the Reapers all together, and do something regarding Cerberus, they are pretty active in the 1st game, though kinda overshadowed by Saren and the Reapers, but they are HUGE in the 2nd book.
I really think a game would be interesting, specially several species. The mixed stigma, of required cooperation, but a huge distrust among species, and of course rumors and misinformation. I think it'd be cool, IMHO. :)