I will list in order of importance the greatest webcomics to my knowledge:
(Please note that I value a regular update schedule more than good art/story/characters/etc.)
8-Bit Theater
The pinnacle of sprite comics, 8 Bit Theater continues to be funny three times a week even after over 1100 comics.
Sinfest
Great art, compelling characters, sticks to the gag a day format and still has storylines. Updates daily.
Cyanide and Happiness
Uses crude art to make crude jokes with no overarching plot or even named characters that aren't just running gags. Updates daily.
Multiplex
Gag a day comic in movie-theater format. Some story arcs become cliche and the characters begin to devolve from funny to serious quite fast sometimes, but overall most comics deliver humor. The author also has a one a week update schedule but consistantly breaks this by adding two or three comics a week. The only comic I know that actually sells itself short when giving a schedule.
Dominic Deegan
Super plot driven comic that delivers its story through endless gag a day comics. This is quite hilarious and serious at the same time. Used to update daily, but is now weekday only, which is still awesome.
Penny Arcade
Gamer comic pinnacle.
Dr. McNinja
Comic book made in webcomic form. Full page comics three times a week. Has recently become full color. Replaces serious plots with hilarity and goddam Ninjas. One of whom is also a doctor. And Irish.
xkcd
Funny jokes. Often math related, though these have become less and less prominent. I also have a personal grievance with this webcomic as it became so completely engulfed by 4chan for a few months that it was almost unreadable. This started off with random memes in a comic here or there, but looking through the archives it is possible to see how the artist becomes increasingly more 4chan oriented until he ends this with a 5 part epic meme loaded finale that finally does away with the 4chan comics. Has since become hilarious again.
SMBC
Gag a day in every sense. Updates daily.
Amazing Super Powers
I cannot think of a good description for this except: funny, over the top, regular updates. It also has hidden panels for every comic. That is just fantastic.
Digital Unrest and Dueling Analogs
Both are funny gaming related webcomics with regular updates, but I feel that Dueling Analogs is slightly superior to Digital Unrest because of the better art that Dueling Analogs has.
Joe Loves Crappy Movies
Movie Review/Webcomic. The odd taste in movies makes the reviews much funnier if a little untrustworthy, but the comics based on each movie are usually clever satires or just something stupidly hilarious. (Just to give a glimpse of this crappy movie love: Joe thought that 'Wild Hogs' was okay if not downright good.)
Awkward Zombie
Gaming comic hilarity.
2P Start
Another gaming comic that spices things up by doing one comic stories revolving around the two comic creators. Both of whom are hilarious and idiotic.
Menage a 3
Stupid. Sexy. Funny. Updates three times a week. Needs no further explanation.
Nerf Now
A comic almost exclusive to doing TF2 based jokes. I love TF2, this is therefore awesome.
Abstruse Goose
Some might say xkcd clone like a bad thing, but abstruse goose only uses a similar, simplistic art style (no stick figures though) and many math related jokes. Even if you think there is a similarity, anything that is like xkcd is still pretty good.
Rock Paper Cynic
Self contained funny strips followed by the author's witty commentary. Very hilarious, witty commentary.
...
And that is it for the greatest webcomics that are currently updating. The best Non-updating comics are:
Sexy Losers
Crudely drawn, sexy comics, each with a funny punchline and storyline.
Concerned
The Half-Life of Gordon Frohman. The man one step behind, ahead of, or to the side of Dr. Freeman for his entire second game.
Gone With the Blastwave
Some of the best art in any webcomic, with a funny storyline and characters. Best military themed webcomic out there.
+EV
The only entirely poker related comic out there. And its funny.
VG Catz
Gaming related. Great art. Great characters. Funny stuff.
And that is about it. Also, while I said in order of importance, its really just the order of my bookmarks, I'm just too lazy to actually evaluate them against each other.