I’m surprised that I am the first to mention Bob the Angry Flower. Dopers will probably appreciate “Bob’s Quick Guide to the Apostrophe, You Idiots”.
Updated every Friday. Huge archive.
Adventurers! is going out with a bang albeit a very long one. If you have a passing knowledge of video games, especially RPGs, you’ll enjoy it. My only experiences with RPGs are the Zelda games, the Pokemon games, and Exile (a random game I downloaded years ago) and I still enjoy it.
The author of Adventurers! has another webcomic called Antihero for Hire about a futuristic booty hunter. Its’ like a funny Batman Beyond only old Bruce Wayne is a redhead with nice boobs.
Something Positive is my personal favorite with Sluggy Freelance coming in a close second. Check both strips almost daily. When I was introduced to both of them took the time to read through each one’s complete archives and do not in any way regret the time invest that cost. Other strips I find funny but haven’t really developed much of an attachment to them. Nothing that comes back regularily at any rate.
I have to make a special mention of [http://www.plif.com/](The Parking Lot is Full) , which has not produced new material in years but was a frequently funny, sometimes insightful, anf often distrubing. The full strip is still on line and is worth the time.
The hypertext in my post above should read as follows: [URL=The Parking Lot is Full]http://www.plif.com/[/TheURL]. Being new to posting I gather I used the controls improperly when trying to set it up. Hope the link works.
I guess that didn’t fix the problem either. Oh well. My apologies
Questionable Content is the best new strip out there.
I put in another vote for Something Positive.
I used to be a big fan of Sluggy Freelance and Player vs. Player, but Something Positive and Penny-Arcade are the only two that I still check up on on a regular basis.
The only two web comics I’ve ever enjoyed is the often-mentioned, Penny Arcade and Pokey the Penguin!
Pokey is the kind of insane genious that only a select few can enjoy.
Pages have been written on the irreverant charm that arises out of its seeming randomness: http://yellow5.com/pp/
To quote the un-official FAQ:
Most of the ones I read have been mentioned before but here they are anyway with a brief synopsis.
Pvp online and Real Life Comics are fine but lately but they haven’t been funny lately. I still read it most weekdays but I never go back if I miss a few.
Ozy and Millie is fantastically drawn and often has some pretty funny storylines. It is currently only being updated two days a week but you can go back in the archive quite a ways. The artist and stories remind me of Calvin and Hobbes (likely because some of the gags were stolen from Watterson in the early issues).
8-bit theater is great fun. I think it is updated 3 or 4 times a week. It is the only one that consistently makes me laugh. GO BLACK MAGE!
Venus Envy a pretty good comic about a young transexual girl. Sometimes it is hilarious and sometimes it is heartwrenching. I wish there were more comics along this line out there.
Something Positive. A truly wicked comic. I particularly like that it is based off of real people and Jhim (one of the characters) currently runs in the background of my circle of friends. He isn’t really slutty like that in the comic (anymore anyway) and he can crochet a mean afghan.
I also read Fuzzy Knights from the good people who bring you Knights of the Dinner Table. It is fun but only updated twice a week (with huge comics by the way). It isn’t great but for some reason I am addicted to it.
For more serious manga styled comics [www.eversummereve.com]Ever Summer Eve is good but you can no longer view the archives without paying for it which makes it hard to get into the story now.
Those are basically the comics I read on at least a weekly basis. There used to be more but I tend to go in phases with other ones. I am at a point where I think I will stop reading the first two I mentioned simply because they haven’t been funny in ages and are almost to the Garfield point of bad in my opinion.
In addition to Venus Envy and Ozy & Millie, which have been mentioned, I’m also fond of:
[ul]
[li]Absurd Notions - updated irregularly lately because Kevin has been having a bad case of artist’s block for the past year or so, but the archives have some absolute gems; Warren’s AOL CD rant is classic[/li][li]User Friendly - mandatory reading for anyone who works in IT infrastructure[/li][li]Ubersoft - mandatory reading for anyone who works with Microsoft products or who does helpdesk work[/li][li]PartiallyClips - really neat gimmick on that one: he draws the same frame three times, changing only dialog between scenes; he guested on Sluggy for a week a while back[/li][li]Lore Brand Comics - remarkably irreverent; artist is one of the Brunching Shuttlecocks people IIRC[/li][/ul]
I liked Megatokyo when it was funny. Now I read reallife.com
No one’s mentioned Wigu or Boy on a Stick and Slither ? Hmm.
Wigu has a backstory but is well worth the read. I’m not sure BOASAS was originally a webcomic, but there’s a new one up every Monday and Friday.
Here’s the list of comics I read regularly, most of which other people seem to like too:
MegaTokyo updates M,W,F
Something Positive M-Su when the author can
Real Life M-F
Least I Could Do M-Sa
MacHall update schedule seems tied to phases of the moon
AppleGeeks M,Th
Under Power M,W,F in theory
Scandal Sheet M,W,F in theory
Penny Arcade M,W,F
Krazy Krow W,F
And I wondered why I wasn’t getting any work done. Anyway, some have rants/blogs attached, some have LJs, some have forums. You can kill lots of time on that bunch 
What a great thread! I’m still working my way through the recommendations but I thought I would add some more to the list.
These are comics with a beginning and a end, rather then ongoing/daily.
1/0
Exploitation Now
Demonology 101
These are comics I’m currently reading (in addition to the wonderful suggestions here).