Some thoughts on possible cities:

Boston: We're all fairly familiar with it and the surrounding environs. Pretty good selection of diverse communities to find characters in.

New York: This feels like the classic setting, lots of places highs and lows contrasts to develop.

Alternately, we could look outside our comfort zones a bit (I'm trying to get into a game set in Tokyo, for example). Moscow? Madrid? Kinshasa? These would all take some research to get into, but could be really fun.

Also, what kind of game are each of you looking to play? Any particular references in other forms of fiction (books, movies, TV) that you'd love to have the flavor of in this game?