The best is a tie between Coach Z and Homsar. Homsar is just completely ridiculous, but Coach Z's mispronounciations (JORB!) are completely hilarious.
The worst is hard to say because all characters in the Homestar Runner Universe and top notch, but I'd have to stick with Pom-Pom. He's a very generic character, doesn't really have a voice, and is always a backup character, and not really center stage.