These are the three that I read regularly:
Dinosaur Comics. It's a strip where all of the panels are the same in every strip, only the text is different. The writing is just so good that it works. Plus, it has talking Dinosaurs. What more could you want?
xkcd. It's a stick-person comic strip with lots of strips about science, math, and computers. Very creative and very well done.
Homestuck. Not really a comic in the strictest sense of the term, as it lacks a normal comic layout and frequently incorporates gifs, flash animations, and occasionally flash games. It is very original and features a lot of well-written characters. It is also extremely long, and takes a little while to get going, but if you manage to get into it, you'll have a very hard time stopping.