It was so hard choosing only a few things to recommend! If anyone else has any ideas, please leave them in the comments!
NBM

Things to look for: To the left is a brand new book that's debuting at SPX and sounds great. I don't know anything about Eric Hobbs or Noel Tuazon, but The Broadcast, about a family dealing with what they think is the War of the Worlds sounds really cool. I definitely want to check it out.
These are the folks who publish Rick Geary's excellent crime books, which I definitely recommend if they have any handy. Old-fashioned block illustrations meet killer intentions in Geary's tales, from Lizzie Bordon to Charles Lindbergh. You might also get lucky and be able to pick up some of the Dungeon series, too. Start with Zenith first, but don't hesitate to experiment. Lewis Trondheim is pretty prolific and imaginative, to boot. They also have books by David B and political agitator Ted Rall. There's plenty of good stuff to be had from NBM, and I urge you to see what books might interest you there.
Oni Press

Things to look for (if they are at the show): Don't worry about Pilgrim, you can get that anywhere. Try some of Oni's series on for size. There's my current favorite, Salt Water Taffy, about two boys learning that living in a land of legends might be the coolest thing that ever happened to them. I've heard nothing but good things about the Crogan Adventures, and was hoping to grab that this year. Like Greg Rucka? So does Oni, with Queen and Country as well as Whiteout. If you like manga-influenced comics with a lot of sarcastic wit, Blue Monday is perfect for you. Best of all, as I mentioned, most of these books are fairly inexpensive, which means you can stock up on a few and pick out your favorites. That's worked well for me over the years, and I look forward to being able to do it again.
Top Shelf

Things to look for: AX is at the top of my want list for SPX this year. I've known about this alternative manga collection for awhile now, since it got delayed a bit in production. It's a chance to see manga that's probably a bit too edgy to end up on the shelves at Border's, and I'm so glad Top Shelf is taking a chance on it. Manga/alternative comics fans need to make this one a big seller, so we can have more.
Speaking of Moore (terrible pun, I know), Alan's zine is going to available as well, Dodgem Logic. I'm really not sure what to think about this one, but I may give it a try. Let me know what you think if you do.
Jeffrey Brown's newest, Undeleted Scenes should be available, though unfortunately he won't be making the trip this year. [Edited thanks to info change.] I'd also suggest grabbing Incredible Change Bots and maybe even Cat Getting Out of a Bag.
I got a copy of BB Wolf and the 3 LPS recently, and can't wait to read it. I loved artist Rich Koslowski's King, and if you can grab a copy of that book, too, don't hesitate. Elvis will thank you.
As you can see, there's a lot out there, and that's just from the bigger names. Tomorrow, we'll examine some of the individual artists I think you should seek out, with some links to past reviews.