Skyfall's pretty cool. Fantasy, two races at almost permanent war, something up with the gods, six artifacts that're probably a key of some sort.

You may or may not've seen, but… Shades of Grey is pretty good, too. Heaven, Hell, a lot of mixup.

Mixed Myth is finished, but pretty awesome. People chase about parts of a dragon, one part tries to take over the world.

Sea of Insanity uses Greek mythology. Mainly follows a nymph who used to date Apollo, Calliope who does duty as her muse, her doctor who turns into a fish, and some guy.

And… it's not really a webcomic, as such, but I wouldn't be counting on seeing it on shelves too soon. Axis Powers Hetalia is worth a look, though your mileage may vary, given it portrays history (the main storyline following WWII) with anthropomorphized nations.

Johnny Walker is a kind of slice-of-life thing. The artist Aido has done some other pretty awesome stuff, and is currently subbing at Applegeeks, which also might be worth checking out.

I must second xkcd!
And to add one that hasn't been posted yet, I absolutely love A Softer World, a one-shot collaborative comic, made up of Emily's photos and Joey's text. It's brief, hilarious, graceful, creepy, macabre, and often thought-provoking. Here is what they wrote in the description for one of their t-shirts:
Here's what's going to happen when you wear this shirt out: A really attractive person is gonna come up to you and say "Oh, A Softer World! I read that too! Man, I wonder what the heck is wrong with that Joey guy, seriously? Who thinks up things like that? Anyway can I buy you a coffee or something -- Oh my God, I'm sorry I didn't realize you two were together! Faux pas!" And then as the three of you awkwardly laugh off the faux pas the person will slip a small piece of paper in your jacket pocket. When you get home you will notice it and unfold it. On the paper will be the following message:
YOU ARE BEING WATCHED

People seem to have covered most of my favorites, so I'll just post a few:

Shortpacked!--set in a retail toy store, the comic mainly focuses on the lives of the cast, but occasionally throws in comics that make fun of various fandoms--primarily the DC comics universe and Transformers, but it includes others. It makes fun of fandoms and fan antics in the way only a veteran greek would know how to do. Screamingly funny, with a spinoff comic posted on Mondays. www.shortpacked.com

The 10 Doctors--This is actually a fan webcomic, but it's so awesome I had to include it. It's a Doctor Who comic wherein all ten regenerations of the Doctor are brought together for unknown reasons and, in typical Doctor fashion, get caught up in all sorts of strange adventures. It captures the spirit of the show perfectly and is a must-read (in my humble opinion) for anyone who's ever enjoyed the show. comics.shipsinker.com/

Errant Story--A half-elf mage decides to take over the world for a school project. On the way, she gets caught up in a rather spectacular adventure. I get the feeling that the authors set out to write a different story than they ended up with, since the beginning is fairly different from the rest of the story, but it's still a pretty great fantasy webcomic in my opinion.
www.errantstory.com

And here's a link for it. It's funnier if you play D&D or at least know some of the terminology.

I also enjoy the following:

Ctrl+Alt+Del (CAD) - Generally a good laugh, even if you're not a gamer (which I'm not).

DAR: A Super Girly Top Secret Comic Diary - Nothing like the title indicates. It's crude, lewd, and pulls no punches on things like lesbianism, nudity, sex, pimples, boogers, and other things normally not mentioned in polite conversation. Also totally awesome.

Looking for Group (LFG) - Funnier if you have at least a passing awareness of World of Warcraft.

Casey and Andy - Ended, so no new comics, but full of mad science and geek humor.

I think the rest of mine have been mentioned already.

~Neshomeh

By Rich Burlew

Adventurers!, which mocks typical video-game traits. Warning: it's way long. As in, there are probably multiple hundred strips numbered 999, and then all the epilogues.

Anti-Hero for Hire, which is about superheroes in a future where Canada invaded the northern United States using genetically altered dinosaurs. It's by the same guy as Adventurers!, above.

Darths and Droids, which posits Star Wars as a role-playing game, and completely subverts all expectations.

Girl Genius, which you've already mentioned.

Irregular Webcomic, which has just about everything. Especially Legos and plastic allosaurs. It's been going every day since late 2001, so there're a few strips to get through.

Narbonic, now ended, which is about a mad scientist's lab. It's rather wacky and very gripping.

The Order of the Stick, which pokes at RPG traits. It started developing a story early, and weathered the transition very well, although Vaarsuvius is annoying me lately.

PS 328, which you've already mentioned.

Skin Horse, which is about a government agency that deals with products of mad science. It's by the same person as Narbonic, above.

Interesting true fact: except for Girl Genius, I got to all of these because I was reading Order of the Stick. Much of that was because it led me to TV Tropes, which has links to just about anywhere and everywhere.

... Catharsis.
http://www.catharsiscomic.com/
Dust bunnies! DUST BUNNIES!

Most of these are snarky, violent, otherwise sick and twisted, or all of the above.

The various works of RK Milholland - my absolute favourites ever.
Suicide For Hire.
Jack.
Concession.

And a few less snarky/violent ones if that's not your thing:
Kevin and Kell.
Friendly Hostility.
Ozy and Millie.
Doc Rat.

I'd also have to recommend looking at the works of

Kid Radd (www.kidradd.com) is quite possibly the best sprite comic you will ever read. Now finished.

Casey and Andy (galactanet.com/comic) is a strip about a couple of mad scientists, one of whom is dating Satan. Sometimes they die. Now finished.

Order of the Stick (www.giantitp.com) should need no introduction. It's about a group of characters in a D&D based world, one of the best.

Misfile (www.misfile.com) - due to a cockup in the Celestial Bureacracy, a guy gets turned into a girl, and another girl loses the last year of her life which she spent slogging away to get into Harvard. Hilarity Ensues. Better Than It Sounds.

Schlock Mercenary (www.schlockmercenary.com) is a space opera about a mercenary crew. Has been updating every day without fail since mid-2000. Well worth the epic archive crawl.

Gunnerkrigg Court (www.gunnerkrigg.com) - a story about a school that has a fairly strong connection with magic, where not everything is what it appears.

No Rest For The Wicked: A very twisted fairytale including a murderous Red Riding Hood, a hillariously sarcastic French cat, and a princess who can be bruised by feathers. Recently started updating again.

Dr. McNinja is a comic about the elder son of the ancient line of the McNinja, who has angered his family by becoming a doctor rather than a ninja, but he still kicks ass from time to time with Ninja Skillz. Excellent comic.

Giant In The Playground, on which Rich Burlew hosts Order of the Stick, an affectionate parody of D&D using stick figures, and Erfworld, a... well, it's an alternate world gaming comic set in a "Safe for Kids" turn-based-combat world. Both better than they sound?

Overcompensating, the Journal Comic with a Seething Disdain for Reality, by one of the coolest dudes in the universe ever, Jeffrey Rowland. It's awesome.
Wigu, also by Jeffrey Rowland, is about a young boy named Wigu Tinkle and his crazy family and crazier adventures.

Questionable Content, by Jeph Jacques, is about a guy named Marten, and his friend-who-lives-with-him-but-is-not-a-girlfriend Faye, and her boss and his girlfriend Dora. There are a lot of indie music references.

Sinfest, a comic about Slick the wannabe-pimp, Monique his love interest, and their friends. And various religious figures. Sometimes NSFW. Sometimes offensive, kinda. Very cool though.

Wondermark, which is hilarious witty captions applied to Victorian engravings.

Looking For Group, which is kind of a parody of all fantasy-world games, featuring the hilariously evilly violent Richard the Warlock.

Dinosaur Comics, which is dinosaurs talking, better than it sounds. Includes philosophy and crazy alternate universes. And Stomping.

Irregular Webcomic and spin-off Darths and Droids. Notable for spawning the phrase "Jar Jar, you're a genius!"