PBF and xkdc are very, very excellent. I follow xkdc regularly, and check back to PBF for updates once in awhile . . . even though there are barely any.
Does Sexy Losers still even exist
pictures for sad children is really, really strange and has a sense of humor that is so in line with my own that I check back every day. It takes a certain kind of person to enjoy it, though, I think. Also, the comics are not self contained episodes - reading a newer one will likely leave you confused unless you have read the earlier ones.
Other gooduns include:
Captain Suppository - sadly no longer updated
Pokey the Penguin
Indexed - not really a comic, per se, but it is smart and funny.