Worst: Gheb (woo bandwagon)
Best: Zoldam, and here's why. I know he isn't going to win, because I have to admit, Schaeffer was one of the best bosses ever, but Zoldam is probably the only generic boss I've ever come across that legitimately scares me. Has anyone NOT had a run on Pirate Ship ruined because he landed a Luna crit? I know it has happened to me maybe 3 or 4 times.