I'm an old-fashioned sort; I won't be self-publishing. I believe in division of labor (it's what pulled us out of the stone age after all!). I believe that people train and work hard to become agents, publishers, editors, etc., and that they have specialized skills and knowledge and deserve their pay. I also don't try to sell my own house, cut my own hair, fix my own car. I'm just that kind of person. I want to do what I do best (write) and leave the publicity to publicists, the design to designers, etc.
If a publisher doesn't pick up my book, I'll just assume it's not a good fit for today's marketplace, and write another, and try again. It's not so important that My Words Get Out There that I am willing to forgo the security of a second and third opinion on their quality.
That said, at some point in the future when I'm flush with cash, I may self-publish some self-help stuff that I don't want to make money on and just want to share with family/friends. Personal experiences etc., life lessons learned, stuff most people wouldn't care about but would still be nice to have in an attractive package.