In order of my personal preference:
1. xkcd - Math, science, sarcasm and stufz.
2. UserFriendly - A webcomic chronicling the antics of the employees of Columbia Internet. Officially ended back in 2007 or so, but I like to read through the archives. Really good.
3. Three Panel Soul - Every single strip has exactly three panels, and they don't seem to be in any order or to be related very much, yet it's the deepest comic series I've ever read. Read it now.
4. Problem Sleuth - If you're up to date on HS you've probably already read PS, but if you haven't go do it now.
5. Homestuck - you said you're up to date on this, requires no explanation.
6. Sweet Bro And Hella Jeff - If you want to catch Down syndrome, this is the way to do it.