Dresden Codak is probably my favourite. Beautiful art style and it touches on some pretty deep stuff (transhumanism?) while occasionally being really damn funny. The Hob story arc is my favourite. Unfortunately, it updates quite irregularly (every month, on average). But Aaron Diaz clearly puts a hell of a lot of work into every panel.
I used to really enjoy Sinfest and XKCD, but they have both been inconsistent as of late. I also used to read http://questionablecontent.net/ but I only have so much soap-opera enjoyment ability in me, even if the characters listen to indie bands and make quips. Still great if you're into that, but you really need to read from the very early ones to understand what's going on and the quality didn't start at the same level.
Yeah, Sinfest went from being quick character-based jokes with occasional 5-10 strip long mini stories to the kind of newspaper comic political "humor" that might as well just put labels on the characters saying what social groups they represent.
Double post I know, but I feel like Bad Machinery deserves its own mention here. Its interesting, especially if you like teenagers behaving like not teenagers, and its written in a more traditional syndicated style, i.e. every page has some sort of payoff to it.