In this regard, Chicago trumps all. Chicago is to New York, as New York is to SF. Normalize this graph for population and you'll see what I mean: http://scienceblogs.com/pharyngula/2007/06/where_are_all_the...
I've never tried living there, but it's a great place to visit. Great food, great museums, great parks, Great Lake. Blues music. You can get there on a train from many places.
Also, 37 Signals seems to be doing OK there.
37 Signals: well, a couple of people live there, yeah. The founder, who was born there and apparently doesn't know that you don't have to live in a crappy town, and DHH, who is from Denmark -- same exact climate, so I'm sure he feels right at home.
Chicago has no soul. It's a bunch of buildings. Visit a town with personality and you'll see what I mean.