HOMESTUCK HOMESTUCK HOMESTUCK HOMESTUCK [http://www.mspaintadventures.com/]
Andrew Hussie is a God of webcomics. Homestuck is the only webcomic so far that has fully used the medium - it includes reader suggestions (well, not any more), flash-based updates with music, frantic gif, a strange parity with a deliberately bad webcomic that's actually drawn by one of its characters, time travel, IM as the main only form of dialog, and videogames.
If you start reading it and feel it's going nowhere, continue to read until the meteor. (You'll know it.) If after that you still don't like it, then it's probably not for you.
Some other suggestions:
Phoenix Requiem. [http://requiem.seraph-inn.com/] Come for the strange magical Victorian but not steampunk world, stay for great character development. It's almost over too, so when you finish reading it it'll probably be over already.
Dead Winter. [http://deadwinter.cc/] The only zombie webcomic that knows zombie webcomics aren't about killing zombies but about human relationships under great distress. Great use of colour and gifs, too.
Kid Radd. [http://www.bgreco.net/kidradd/] If you read only one sprite comic... well, read 8-bit Theatre, but if you read two, the other one'd better be this one. Although whether or not pixel characters are 'skilled artwork' can change; they are all original characters in a variety of styles, though.
All of my other picks have already been suggested, so there you have it.