It does; one nice thing about SF is that it's got a pretty sizable downtown, with some pretty high skyscrapers (much higher, say, than the pint-sized ones of Boston, or the non-existent ones of DC), but also has lots of other, very varied neighborhoods. Also, you've got the legitimately still-gritty and grungy Oakland just across the Bay. Fincher got some great mileage out of our Financial District in The Game
, for instance.
Sure, Chicago could probably also work, but while it's got some great downtown areas, as seen in Transformers DOTM
, I haven't really gotten the sense that its non-downtown neighborhoods are all that special or distinctive.