I'm just 20 minutes from the city (lil) and I'm in manhattan at least weekly. I'm down for a meetup if you're sticking around but this weekend is SATs for me :( In terms of stuff to do, you should hit up Chelsea (that's Chelsea market, the galleries, HighLine etc.), and then go down to SoHo to get your hip on. Careful though, there're some mighty snowstorms a-brewin' this weekend. If you've been to all the big museums, but you enjoy museums, I suggest the Frick Collection and the Morgan library for some kick-ass old shit. The Morgan is the crib of J.P. Morgan and it's pretty freakin' awesome. Otherwise, I super super duper suggest Dizzy's Club CocaCola for the absolute greatest jazz in New York today, for real. There's a ~$48 cover charge for a table I believe, but I know the manager and will likely be able to snag some swanky seats for free were we to have a meetup with two more people. Keep me posted!
edit: Other dope-alicious areas to hang out, especially if you're planning on hitting bars: >bowery (below Greenwich/East Village, but if you're getting close to Canal St. you're getting too low and should head west) >Tribeca (nearby the bowery) >west village if you're mellow, french, or happily obnoxious, or east village if you're pompous and lame