I'm reading Amanda Hocking's blog--she's a successful self-published writer, and all of 26 years old. She makes a good point here about something that I think people worry about unnecessarily: There's no reason to worry that you'll alienate traditional publishers if you sell a lot of copies self-publishing. On the contrary, if you are successsful, you'll have more appeal because you will have established a track record for yourself as a writer who sells a lot of books.
This has always been true. Heard of Bridges of Madison County or What Color Is Your Parachute? Self-published, sold a lot copies, picked up by a publishing house. Terry McMillan? A self-published author who sold a lot of books and got a contract with a major house. The so-called stigma of self-publishing didn't apply, because there was money to be made. The real stigma with self-publishing was that self-published books tended not to sell well. That could be because of quality issues, or it could be because the book's topic was esoteric, or it could be because the book's author lacked access to a major distributor and wasn't willing to hand-sell out of the back of their car the way McMillan did.
I think people who worry about "stigma" are once again forgetting that publishing is an industry that needs to sell a lot of books, not some sort of quality-control board for an academic literary salon.
(For the record, J.A. Konrath thinks you shouldn't worry about alienating traditional publishers anyway, because nowadays you can make more money self-publishing.)