First off is the comic I've been reading the longest: Cyanide and Happiness.
They're an extremely funny group of guys with a theme of unfortunate turns of events. They release comics and are starting to release short animations too. The best part? The release every day! Characters include the Purple-Shirted Eye-Stabber, Seizure Man, Premature-Ejaculation Man, Super Jerk, and the Incredible Sulk. Give them a visit or subscribe to their RSS at http://www.explosm.net/.
Next up is another great: Amazing Super Powers
Wes and Tony release a new comic every Monday and Thursday. It's hard to tell what to expect from this comic, seeing as it has almost no plot. In fact, a plot will run for three comics at the most. When you scroll over a comic, you get a witty comment or extra quip, and to the right of the top right corner is a secret link to a secret comic. It's usually a rewrite of the comic with alternate text or an extra panel. Their website is LOADED with extra content, so be sure to check it out. The URL is http://www.AmazingSuperPowers.com (bet you wouldn't have guessed that one).
The last comic I'll mention in this post is Buttersafe:
Buttersafe has no ongoing plot, but it's always good for a giggle. Many of them leaving you thinking ".. what did I just read?" but with enough thought it'll plant the seed of curious laughter in your brain which should grow and flower just in time for the next comic to be released. Every Tuesday and Thursday, Raynato and Alex will plant their seed in you. Or something like that. Drop by at http://buttersafe.com/.
I hope one of these sparked a fancy and that I've turned you on to something to look forward to every so often. I've got a few more comic sites but this entry is long enough and it's 2 AM. Let me know if you liked any of these, you've got a better comic, or even if anyones reading this..