My personal issue with YComb's approach is that they actively (via this site, for instance) promote engineering mediocrity. Remember posts "PG made me drop out of college today!" ? I have seen several of those. Web 2.0 is all about this: cheap&quick high-school level programming project done over a weekend, polluted with google ads with mandatory "blog" attached to it.
To me that is sad, There is nothing "glamorous" about it. My major in school was AI, and our professor used to dream alot about more powerful hardware that was supposed to become a reality soon. Well, it became. And for what? To run 8 Mongrels with some quick&dirty Ruby scripts converting contents of 4 DB tables into nicely looking HTML with roundeed corners? What a waste...
But does an iPod engineer understand any AI? Probably not. Steve Jobs made stupid comments in his presentations (still remember the "branch prediction... it predicts branches!"). But he has an eye for opportunities that not even your professor can boast having. If there's a market, and you know what it takes to supply it, supply it. In my view, YC is addressing this; it may saturate quickly, but the need obviously exists. If your expertise targets the extremely educated, by all means make something that satisfies them.
But don't forget that there are a lot of people to please. Just please the ones you understand, or think you do. I'm completely taken aback by twitter's success, but hey, people use it, what can I say.