I've been attending RPG cons since I was ~10, but I didn't attend my first (WI) GenCon until the '90s. I grew up on a steady diet of local east coast, regional cons, and find that I really enjoy that size and focus the best. When I lived in San Jose, CA, I hit many of the local cons there, and I miss that (there aren't cons in Wichita, and while KC is close, the few cons there now aren't that hot from what I've heard).
I try to attend DunDraCon whenever I'm able to be in San Jose in February for work trips. I missed this year, unfortunately, but it's a lot of fun (more so than KublaCon, FYI). When I was there last (2008), I played Cosmic Encounter for the first time, which was a wonderful afternoon well-spent in one of DDC's myriad pick-up games!
This year I'm attending
GaryCon in March, and the
North TX RPG Con in June (for which I just completed my event registration

). Both are small (~200 attendees or so vs. say DunDraCon's ~1500), and old-school-focused, so I'm sure to find games I want to play/run.
I've found GenCon Indy to be a double-edge sword: I like going, and love getting to see folks there I don't otherwise see, play games, hit the auctions and exhibit hall, etc., but in general I find GenCon to have grown beyond my willingness to attend regularly as a gamer. From a publisher POV, I'd like to be in a position to exhibit there again sometime, but that's in our future for now. When I do attend GenCon, I try to dig into board games, minis companies, and the various smaller press RPG publishers vs. WotC, D&D, and the usual behemoths.
I attended the first DragonCon in 1987 and returned to it several times in the '90s, although I haven't been back since then. I'd enjoy hitting that again, I'm sure. Ditto for Origins (last was '99). Both are considerably larger now than when I last attended, I'm sure, though (DC was already pushing 10K in the late '90s, but Origins was still ~5K although it's grown in recent years to be pushing ~10-15K I think).