Bit late, but I couldn’t not mention the first web comic I really pored over, the now ended The Perry Bible Fellowship.
Although much as I love it, I had Google “Go eat a dick truancy bot” to even remember its name :o
Most of the ones I find worthy of recommending have already been recommended. Some that I read, I really can’t pass along with a great deal of enthusiasm.
But thank you all, for leaving me to link to Lovecraft is Missing. And thanks to Randy “Something Positive” Milholland for turning me on to it. 
Two things: I don’t know why page one shows the set of panels twice. And if you start feeling like Billy Pilgrim now and then, don’t worry, it’s just the way the story is being laid out.
I love to clog my email inbox - which of these can be subscribed to?
One that LiM’s author recommends is The Secret Knots. I found it worth a read, if a bit twee.
For some reason, I really like the dork adventures going on with the little late 80s scam artist hero of Wizzywig. The story is meandering and the art is strongly reminiscent of R. Crumb, but I keep up with this one. You might like it too if you remember pirating games that came on 5 1/4" floppies and racking up big phone bills calling a cool BBS.
DM of the Rings was actually directly followed up by Chainmail Bikini, which was by the same authors with the same characters—it sadly was cut short due to behind-the-scenes stuff, but the authors did a nice job giving a text summary of the planned ending, and a bonus “epilogue” strip when it was reposted.
Anyways…
Unspeakable Vault (Of Doom) is very cute, if you’re a Lovecraft fan.
Bogleech Comics is…well, I think it’s what something FROM Lovecraft would write if they did a webcomic.
Space Avalanche is fun, and a tad twisted. When it updates.
JACK Home Page - “Book For You”
Heard about it first here a while ago. I had to start reading from the start though to understand what was going on.
A future earth with genetically altered animal/humanoids complete with heaven and hell, angels and demons and aliens. Can be NSFW occassionally. I am addicted.
A notoriously grim webcomic; I’ve avoided reading it because I’m depressed enough already with the world.
“Occasionally”?
I mean, don’t get me wrong, from what I’ve read of the comic (about five years ago), it was of good quality and well told, but Jesus! What was the stuff without un-worksafe, unrelenting horror? The white between the panels?
I-I-I-I dunno about “grim.” I’ve just finished with the first thousand of them. There are quite a few dark moments, true, but the story arcs almost always conclude with a shot at redemption.
The premise does assume a buy-in to a lot of the monotheistic concepts associated with western civilizaton, but that doesn’t have to ruin my enjoyment of some pretty good storytelling.
If anything really threatens to take me out of the story, it’s the author’s cavalier attitudes toward spelling. He does seem to be improving on that front lately, though.
To add to the already listed i like Hijinks Ensue
The podcast is quite good as well.
My regulars (some mentioned earlier):
Axe Cop - as mentioned, a comic about an axe-wielding crimefighter, written by a 5 year old. So awesome.
Hark! A Vagrant - comics (largely historical in subject matter, though sometimes literary and sometimes whatever) by Canadian cartoonist Kate Beaton
The Original Laugh-Out-Loud Cats - comics about two hobo cats, Kitteh and Pip; drawn like it’s from the Pogo era, but with internet/LOLcat/leetspeak jokes
American Elf- an autobiographical daily comic that goes all the way back to 1998. Pretty wicked.
ETA:
Unshelved - a comic about librarians. Brutally funny, if you have any interaction with that world.
Piled Higher and Deeper, a comic about grad students. Funny if you’ve ever been to college, in my opinion.
Concerned, a comic about whoever that guy was who wrote all those letters to Dr. Breen in Half Life 2. Friggen hysterical comic.
Terminal Lance. I can’t remember if I recommended this already, but it’s a comic about the Marines, drawn by a Marine (so like a cruder, more offensive Marine version of Air Force Blues)
Homestuck: Riveting, funny, and deep. The author is simply amazing at characterization, able to build a rounded and memorable character from nothing and with nothing. It also has one of the most intricate plots you’ll ever find, without dragging too badly (although with all the scene-switching, you may find yourself missing certain characters over stretches). This one is definitely worth sticking through if you’re the kind of guy who reads all the time. Be warned, though–it is not light reading.
Brawl In The Family: Perhaps the only family-friendly webcomic out there, it still manages to be funny and hard-hitting if you’re a fan of Nintendo video games. Also has an unusual amount of “awww” (cute, not sad) moments.
Keychain of Creation: An Order of the Stick imitator that managed to take off on its own. The pacing is just brilliant, with every aspect–scenes, lines, plots, characters–going on as long as they need to, and no longer.
1/0: The nothing that just kept. on. going well past the point where any sane man would have said “stop”. It’s a good thing the author was quite the philosopher, or it would have been soul-crushingly boring. As is, though, it’s a curious little treatise on God and His relationship between His creators. (This one has ended)
Slightly Damned: An adventure comic featuring an angel, demon and resident fantasy creature on a journey to figure out just what in the hell is going on with…hell. It has a fairly standard plot, as far as adventures go. It does have really nice art, though (currently it is in a flashback, which are deliberately drawn sketchily). Note: not a furry comic.
Brandon Bolt, the writer and artist of Nobody Scores, has sort of resumed doing Nobody Scores. I say “sort of” because he’s doing new comics perhaps even more irregularly than before the hiatus, and his comments are definitely expressing much angst.
Not truly a web comic but a graphic novel presented as a web comic by the inestimable Phil Foglio Buck Godot:Zap Gun For Hire
Might I also suggest Troops of Doom not a web comic but a diorama type thing with really no point involving figures from Star Wars, GI Joe and Legos…