I happen to be partial to the $50, probably because they seem rarer than the $100. Though the $100 is certainly more useful if you just want cash for an emergency. I've never encountered a place that refused to break a $100 (unless they didn't have enough cash in the till yet...I had to refuse one when I worked at a bookstore in high school and someone wanted me to break a $100 first thing in the morning), and often overseas a crisp $100 bill is the only denomination they'll take.

I think they discontinued the 500 euro note because they found most of them being used were being used by drug dealers and other criminals.