I pretty much always save up the Master Ball for Mewtwo, since most other Pokemon usually aren't too hard to catch. If one, usually one of the birds, is causing me problems though, I may end up using it on that one. I've used it on Zapdos on several occasions, so yeahh :p One of my friends also used it on a Fearow once, in my game mind you, because someone had told him that it was the legendary Grass bird hnggg.
Anyways, my latest one would probably have to be Mewtwo. There's not a whole lot of legendaries to go around, and considering I never encountered the legendary beasts a single time in my game, they're kinda out of the question. And yeah, Mewtwo is definitely the hardest one to catch by regular means :p