xkcd has been amusing me for several years now, although it is really nerdy.

Achewood by Chris Onstad is the undisputed best webcomic out there.

http://www.achewood.com

PBF was my favorite, but it's over now.
http://pbfcomics.com/?comic=random

I enjoy when pictures for sad children comes out, though it's even more esoteric:
http://picturesforsadchildren.com/index.php?comicID=77

http://mycardboardlife.com

this is the sweetest little series made by a gal in England. I LOVE IT!!!

Oglaf Comics.

Funniest comic I've read in a long time.

Hark! A Vagrant is a fabulous comic for nerdy history/literature jokes.

http://www.harkavagrant.com/

scarygoround.com is probably my favorite right now (mostly the old archived stuff). I still remain to be convinced of John's new work (Bad Machinery).

Also, qwantz.com, because T-Rex is a badass.

Saturday Morning Breakfast Cereal (SMBC): http://www.smbc-comics.com/

By far my favorite of all time - I sat and read this entire thing in a single weekend and only wanted more.

The Order of the Stick:

http://www.giantitp.com/comics/oots0001.html

Wow, no one has mentioned Axe Cop? Surprising.

As a description, it's a comic drawn by one of two brothers and written by the other...who happens to be in grade school.

It's quite hilarious at times. Check it out.

http://axecop.com/

Three current faves:

something positive
Girls with Slingshots
A Girl and Her Fed

Nerf This is growing on me, it's only been around a year though so the archive isn't that deep yet. (Probably a good thing if you're trying to catch up.)

I just love comics that take their time to develop their characters into three-dimensional creations. The fact that all these comics tend to feature characters with a little social devience just makes them more fun.

Marvel Year One on WebNation.com

Cyanide & Happiness.

Nedroid's Beartato & Reginald comics are a consistent delight. His Twittered "Lost" comics (spoilers) he was doing each week after the show were always hilarious, too.

Steve Wolfhard's Cat Rackham is really fun, too.

xkcd is pretty good, but the security system on my home computer tells me, "DON'T GO THERE!" whenever I try to look at it. So I don't see it often, though I can look at it at the library OK.

I don't suppose this really qualifies, since it's a newspaper comic, but I can only find Brooke McEldowney's "9 Chickweed Lane" on the Internet. I read it at the Houston Chronicle's "build your own comics page" (approximate name) site. For the past few months, he's been telling a wonderfully romantic WW2-era story about an American singer and a German POW. "9CL" has been my favorite on-going story strip for the last several years.