I'm currently living in Pennsylvania, and I think there are a few options open to the area.
A friend of mine suggested Pittsburgh as it is a bit of a crossroads into neighboring states, plenty of colleges and museums, interesting architecture, odd streets (and anyone who's ever relied on a GPS in that city knows the feeling), and it's own legends (anyone else here familiar with "The Green Man?"). Let's not get into the industrial side of things; not as bad as Chicago, but some fodder is there.
My usual local players wanted to turn Reading, PA into this kind of game. Plenty of social issues, gangs, crossroads for illicit item trafficking, stones through from some wooded areas and farmland, etc. I can see it, but meh.
One of my former flatmates suggested Philadelphia, relying upon the history and various symbols (many compasses scattered around, supposedly).
I'd kick around more ideas and elaborate, but it's time to close shop. If I get the chance, I'll see what I can add to these to make a bit more sense.