Boxer Hockey by Tyson Hesse (T, ongoing)
Follows a particular team playing the unusual sport of Boxer Hockey, wherein 4 people strip to their undies and use a frog as a ball. Also, there are no rules. The comic is more about the teammates then anything, with the occasional oneshot joke thrown in that really has nothing to do with the story. Features ludicrous humor on just about every subject and more than a few sojourns into the ridiculous side of art styling, often with hilarious results. Just a warning: put on your South Park goggles everyone. Yeah, it's that kind of humor. Updates are Sun. and W, though this varies depending on the artist's schedule.
Cucumber Quest by Gigi Digi (K, ongoing)
An adorable little comic following the legendary (if unwilling) hero Cucumber and his much more enthusiastic little sister Almond as they battle for the freedom of the Donut Kingdom from the evil reign of Queen Cordelia before she summons the terrible Nightmare Knight. ...And they live in a place called Caketown. Yes, it's that adorable. Reads something like a particularly funny children's book, with every character themed on a certain type of food. Updates are supposed to be Sun. and W, but tend to be every other day.
Girls Next Door by Pika-la-Cynique (K+, ongoing)
Though technically not original work, this had to be included. An offshoot of another popular DeviantArt comic, Roommates, in which Jareth the Goblin King (Labyrinth) and Erik (Phantom of the Opera) are roommates in an apartment building populated by their female counterparts as well as many other fandom favorites. Girls Next Door instead follows Sarah Williams and Christine Daae as they battle the evils of fanservice and bond over being unfairly attracted to highly dangerous men. A truly ingenious idea that just keeps getting better. The many, many crossovers are all done very cleverly and fit well within the storylines. I also credit this comic with introducing and getting me hooked on no less than 5 new fandoms. Oh, and the art is gorgeous. Updates every Wednesday.
Goblins by Tarol Hunt (M, ongoing)
A very long, extraordinarily brilliant comic based roughly on Dungeons and Dragons looking at the world through the eyes of the experience-fodder goblins. I've never played D&D before and I still find the humor very accessible and very, very funny, so don't worry about it if you haven't. The style is very interesting and unique and goes through quite a metamorphosis near the beginning so if you don't like it at first, keep reading and give it a chance. The story is incredibly detailed and obviously well-planned with tons of drama, humor, and outright horror to give it a very nice well-rounded feel. Updates are every T and F.
Hanna is not a Boy's Name by Tessa Stone (K+, ongoing)
A wonderful little comic following the gungho, accident-prone paranormal detective Hanna and his new partner, ... (a zombie who doesn't remember his name, so Hanna calls him whatever he feels like at the moment). Features all manner of familiar paranormal creatures and situations along with more obscure ones. The art is wonderfully chaotic and colorful, yet still manages to convey a dark and somber mood. I don't know how she manages it. Updates whenever, usually once a week at least. Currently under hiatus.
Head Trip by shinga (T, ongoing)
A comic that follows whatever storyline it feels like at the moment. There a few central characters that are very roughly based on the artist's family and friends and also a few unlikely superheros (Emokid and Chemokid) that the narrative switches back and forth from. Occasionally pokes fun or outright tears down popular books/movies/tv as well as real people/politics/whatever else the artist has a problem with. Mostly I agree with her and if I don't I can see where she's coming from, so it ends up funny either way. The art is drawn in a wonderfully fluid cartoon style that I always like to come back to. Updates are M, W, and F with occasional unexpected hiatuses thrown in.
Lackadaisy by Tracy J. Butler (T, ongoing)
If you're going to read any comic on this list, for God's sake, let it be this one. Set in St. Louis during the Prohibition Era, our feline heroes (...or protagonists is probably better, since this is a morally gray world) set out on a quest to survive and keep the old Lackadaisy speakeasy alive. The comic is brilliantly detailed (background porn, anyone?), incredibly well-researched, and has a plot that just keeps getting better the deeper you get. A fantastic read that you'll come back to again and again. Updates are usually once a month, with 3-4 pages each time.
The Meek by Der-shing Helmer (M, ongoing)
Another amazing epic that has many more years til completion. Angora, a strange girl with unexplained "nature" powers, Luca, a powerful emperor of a barbaric nation, and Soli, a desperate woman who just wants to see her ex-boyfriend die, all have something in common. Of course, we don't know what that is yet, but it's sure to be something world-ending-last-hope-for-mankind, right? An amazing read, everything flows so well and is just so gorgeous, I can't even describe it. Updates whenever the heck it feels like it, but usually more frequently than not.
Roza: the Cursed Mage by Kelly Hamilton (K+, ongoing)
Details the story of young Roza, a mage branded by a mysterious curse, who is determined to get rid of it by any means. A lovely simplistic story that reminds me of classic fairy-tales, with the exception of a strong female protagonist of course. Nice expressive art and an engaging story and characters. Updates W and Sun.
Yet Another Fantasy Gamer Comic by Rich Morris (M, ongoing)
The longest and most detailed comic I keep up with. And there's a reason for that. The story follows basically the entire world at one point or another, though home base is technically in the Black Mountain with the "evil" creatures that live there. Characters include goblins, drow, elves, men, halflings, liches, orcs, mindflayers, beholders, and all manner of other species you could ever think up. And even though it follows approximately 20 storylines at once, it still manages to be coherent and easy to read. Just brilliant. Done in grayscale cartoon sketches with about 120 different recognizable character designs. And that's just an estimate. Updates daily, and has done so for almost 6 years now.