First tier (in alphabetical order):
Absurd Notions (sample) - joke-per-strip, extended storylines
Goats - joke-per-strip, extended storylines, rather weird
Penny Arcade - joke a day gamer humor
First tier, infrequently updated or inactive:
Bobbins - inactive (finished), joke-a-day, British humor, often a touch of oddness
Scott McCloud's Morning Improv - inactive, independent long-form stories, panel-per-day
Leisuretown - long form, total insanity, infrequent updates now
Return to Sender - quirky long-form story, currently infrequently updated but hopefully will get going again soon
Strings of Fate - long form anime-influenced comic, recently went on pause?
ZWOL - no longer updated regularly, long-form, spotted him because he hosts Scott McCloud's reinventing comics forum, and I like his blog (he posted lots of links post 9/11 that showed me I was not alone)
Second tier - I read these inconsistently, or they're inconsistently funny, or I read them but I don't know why or doubt I'd recommend them
College Roomies from Hell!!! - joke a day, very extended mutant/superhero-soap-opera storylines
Diesel Sweeties - joke-per-strip, super-pixelated art, some of the humor doesn't appeal to me
PvP - joke a day, sometimes multi-day storylines
Sinfest - joke(?)-per-strip, several independent/semi-related sets of characters/storylines, I only like half of them, but nice art
Modern Tales - this is a pay site that lets you read the most current, so if you're careful you can read it for free. I paid for a year.
Cuentos de la Frontera - long form
Makeshift Miracle - long form, the main reason I signed up for MT, but it's going way too slow
Odd Jobs - long form
Patent Pending - long form, more story than humor, by the author of Goats, infrequent updates
I also used to read Wedlock and Kid Clango, by the authors of PvP and Diesel Sweeties, but neither of them have updated in a long time.
And then there's the not work-safe Sexy Losers, which is way, way TMI sex comics (nudity, explicit sex, necrophilia, edges of incest) that uses its outrageousness as the crux of its humor, in some sense.