Ctrl-Alt-Del
Webcomic and commentary on video games and other cultural references following the antics of Ethan (obsessive gamer extraordinaire) and Lucas, the more grounded roomate who remembers to call emergency services whenever Ethan does something... well, Ethan-esque. Along with an ensemble cast of very entertaining characters, CAD provides a humourous escape.

Girl Genius
Webcomic that describes itself as "gaslamp fantasy" which centers around the adventures of Agatha Clay in a world full of people called "sparks" who are geniuses with the ability to design and build incredibly complex machines. Good fun, good characters and novel in that it has a strong, likeable woman as the main character.

Least I Could Do
Follows the hilarious, off the wall antics of Rayne Summers, a man who views life with sex as his primary motivation, and his varied friends and family. From the same team as Looking For Group, this comic never fails to make me smile with updates everyday. Sunday's comic takes a different approach and shows Rayne's adventures as a child.

Looking For Group
Looking For Group is a Fantasy/Science Fiction parody comic updated several times a week that follows the adventures of a group of well-written characters that push the bounds of their genre stereotypes. It pokes fun at everything in these genres and anything else the authors enjoy.

MegaTokyo
Webcomic about Piro (artist, manga/japanese stuff enthusiast) and Largo (hardcore gamer and 'l33t h4x0r'), two friends who fly to Japan on a whim, only to find themselves stranded. Experience Tokyo from their two unique and very different perspectives every Monday, Wednesday and Friday.

Penny Arcade
Webcomic put up most days by two guys who give their two cents on the latest and greatest that comes out in the gaming world. The snappy, usually standalone comic is usually a humorous poke at something in the gaming industry, following the opinions of Tycho and Gabe.

PVP Online
Follows the crew of a magazine called Player-vs-Player. Intermittently has commentary on the goings on in the world of video games, but mostly tells the stories about the people. Pretty funny and updates everyday Monday through Friday, with an extra feature called 'Ding!' on Sundays.

Sinfest
Webcomic put up everyday that follows the various adventures of Slick, Monique and friends, God, the Devil, Buddha, Jesus... to name but a few. With some hilarious commentary on society occasionally thrown in for good measure, I always enjoy this webcomic by Tastuya Ishida.
The official RSS is a bit weird and has no images, so I made this one - enjoy!

VG Cats
Webcomic and commentary on video games and various other cultural references using satirical cats placed inside of a comic version of games, movies, anime or other media. Generally pretty funny stuff, although I tend to just go for the comics, rather than the accompanying commentaries.
The author also writes a Pokémon parody called Super Effective, which is updated very occasionally.

xkcd
"A webcomic of romance, sarcasm, math, and language."
That about sums it up, actually - updated every Monday, Wednesday and Friday, it's very geeky in all kinds of pleasant ways.