The one I still read reguarly which I've read the longest time (almost 10 years, now) is Sinfest. It's hard for me to say what it's actually about, as it has several themes, but a limited set of characters.
Another I've followed for a long time is Freefall. It's science fiction. Funny science fiction and quite realistic. It's remarkable for how many strips it takes to go through one in-comic day. Now it's 1800+ strips and I think only about two weeks have passed.
Schlock Mercenary is also science fiction.
More science fiction: Zeera the Space Pirate. It's finished now. Well worth reading.