I'm not the most social person to begin with, so I gave it a lot of time, but I just totally failed to make any non-work friends because of stuff like that. I've been here for ~4 years and am so ready to get out West. Of course, it's never as easy to move that far as you'd want it to be.
I remember in Cambridge I could swing downstairs to the neighborhood bar, find a stranger, and strike up a conversation. Maybe it didn't work half as well as I am recalling, but even then, it was better than DC, where it always turns to "where do you work?" And "a startup" has only slightly more cachet than "I'm unemployed."
From a professional standpoint moving here has been great, but from a personal point of view, I think it's the biggest I've made.