Here in San Francisco, I see gender-variant people all the time. But with all of the gender spectrum represented, it's impossible to tell who's what just by looking at them. I don't happen to know anyone who's transsexual and is open about it, but that's probably because I don't hang out in the LGBT scene. I know people through music, work, my neighborhood, and the local bar. Really a pretty eclectic group of people. I know a few of people who might be trans, but I would never say anything about it. It's none of my business.
If I met someone who I knew was trans, I might talk to them about it, but it would depend on the person and how comfortable I was around them. I'd almost definitely talk to an FTM, especially a gay FTM, because we'd have that in common, and I've never met an FTM before (well, chances are I have, but I mean someone who I knew to be FTM). I'm shy around girls, though, so I'd be less likely to talk to an MTF about something so personal.