I was all set and ready to dislike Epic Rap Battles from their view counts alone, but man... those are some high-quality videos. Costumes, accents, green screen... not to mention funny, and the best part is that they almost always give both sides some good lines against the other.
I can't recommend 4PlayerPodcast anymore. It's really too bad, but I honestly don't find it entertaining the vast majority of the time anymore... and that's just watching the Highlights! Watching the actual feed drags a lot more.
No, my true Youtube love is Two Best Friends Play (or better yet, Super Best Friends, which includes Woolie and sometimes guests). They were a little more gimmicky at the start, with more editing and playing up their respective personalities, but it turned out to not be necessary. They ALREADY act like that, and they're already hilarious (although of course the played-up episodes are hilarious too, see Vampire Rain and Shadows of The Damned). The way they talk to each other, their in-jokes, it all makes you feel like you're in the room with them, and you have fun. Their full playthroughs are just as much fun for me, if not more so, than their condensed, for-the-masses Machinima series. Matt and Pat, I hope you read the Escapist too!
Aaaaand... hm, Gabriel Iglesias? He's an amazing stand-up comedian, although I never liked DAMN TV... and of course I should think we all love anything by James Rolfe (the AVGN). Although, I usually watch his website, not on Youtube.