1. Mobile. Facebook does have one of the top mobile apps on the planet, with its iPhone app at the top of the download list for quite some time. But I think it's fair to say Facebook doesn't really care about mobile; the iPhone app languished with overt bugs for half a year before they fixed some of them recently. They have no iPad app. They no longer innovate in this arena (more on that next), and while that probably won't be the case forever, there's a great opportunity for a network with a best-in-class app to take the lead here.
2. Innovation in social. Take, for example, geolocation. Foursquare and Gowalla have definitely found some new niche that will be here to stay: people like to know where friends are, where the currently happening thing is. I've tried those services three or four times each and, while interesting, still aren't compelling enough. Facebook has done nothing here. Yet.
3. Out-facebooking Facebook. I'm a member of the initial Facebook group: my school was something like the fifth school on the site. Things have changed dramatically from those humble beginnings. It's much harder for me to cut through all the Facebook app bullshit today and actually find out what's going on with my friends: status updates, photos, events, that sort of thing. Things that actually matter. People still will want to play games, but I think there's a huge part of the population that just want a clean, social network again. I've expanded on this on a short blog post last month, if you're interested in reading more (and I apologize if you're not): http://zachholman.com/2010/05/rebuild-facebook
While I don't think Facebook will die a Friendster death in a poof of magic scaling sprinkles, I do think there's opportunity yet for a small outfit to out-innovate them, out Facebook them, or just otherwise carve a lucrative niche for themselves in the market.