We've all seen the Ask commercials demonstrating how much more user friendly their search is. But, a commercial is one thing and reality is another.
It's really a matter of optimizing for the big three (Google, Yahoo, and MSN) and letting everything else fall where it may.
If you have a website that is well designed and content rich, it is sure to please almost all major search engines. What's more, you are likely to build a significant portfolio of search terms where different terms attract traffic from different search engines.
But, spending your time trying to please every search engine is an exercise in futility. You're better off spending your time optimizing elsewhere.