Whee! I will copypasta my reply to someone else asking this same question!
Homestuck is a sort of web comic done in MSPaint style. It's mainly the story of four different kids who all play this immersive reality game called Sburb, and a lot of crazy stuff happens. There's another "side-story" (I can't really call it that, because it also becomes a main focus of the plot and ties in with almost everything that happens) with these aliens called trolls that contact the kids while they are playing this game, and end up playing a crucial role in its development and outcome.
There's lots of time travel and paradoxes and jumping back and forth and it can actually be almost frustratingly confusing to read. (I can't even do any of it justice trying to explain. You can't even really explain it to anyone. o____o)
I like it because of the style it's done in, and the story is so widespread and massive. The characters are interesting; some of them I outright hate and others I really like. The fanbase tends to turn a lot of people off, though, which is understandable. I stayed away from reading it for a long time because of the fan base.
Another thing that makes it really neat (I'm adding this on, haha) is the fact that it's not comprised solely of still images to tell the story. There's elaborate flash animations - some of which you can actually control and interact with, like a video game - a whole set of music created specifically for the series, and moving GIF images; not to mention the amount of sheer detail that is put into the drawings and the backgrounds. They seem like simple sprites but if you take the time to appreciate all that is put into nearly every panel of the webcomic, it's pretty incredible. C:
If you ever want to take a crack at it, you can visit mspaintadventures.com and check it out. The first panel is right there on the front page. 8D