I don't play M&M, but I do play Champions (gasp, a non-D20 game). We've almost exclusively played in "real world" cities. NY is the first, but we live near it to get details right. After that it's been all over - West Coast, Atlanta, etc. Very easy to get maps and prominant points - just write the tourism board for a vacatioon packet. (Okay, much of this gaming has happened before the WWW was around.)
Now, a bit of work fitting supers into our world plan may suggest changes to cities, if supers have been around for a while. The current campaign is a emerging powers game set soon after 9/11 where super powers didn't exist previously. Very interesting.
Cheers,
=Blue