Obvious ones out of the way: The Oatmeal, XKCD, Cyanide and Happiness are all great but we all know about them.
A couple of my favorites:
1. Poorly Drawn Lines
Really absurd, kind of dark humor.
2. Sarah C. Andersen
Superbly relatable/adorable. Also updates with her very impressive illustration work (she's a student at MICA).
3. Formal Sweatpants
About as self-deprecating as it gets.
4. Dresden Codak
Not humorous. These are bigger, follow a story line and usually span multiple years (because the dude takes forever to update). I spend about 30% of every day wishing for updates to the Dark Science saga. Most are too big to post here but here's an example of some of the stunning artwork:
Do you guys have any favorites? If so, which?