I'll second PVP, Real Life, Penny Arcade, Sexy Losers, and the Perry Bible Fellowship.
http://www.aikida.net - Storyline about a chick named Aikida and her on-again/off-again boyfriend Wade
http://www.goats.com/ - Zany awesome story about everything imaginable. You have to start from the beginning. This is BY FAR my favorite comic.
http://loserz.scribblekid.org/ - a little random and immature at times, but it's a story about 3 kids in high school who are best friends nomatter what.
http://www.questionablecontent.net/ - Another one that you have to read from the beginning. QC stars a nerdy indie guy named Martin who has serious problems with women. The author's art has gotten amazingly better over time.
http://www.spamusement.com/ - HILARIOUS comic based entirely off of spam email subject lines. Terrible art, but it's the funniest shit ever.