The premise of Tom Goes To The Mayor is easily summed up in that title: Every episode, Tom Peters, Jefferton's resident entrepreuer goes to see the Mayor of the town with an idea for improving life in Jefferton, an abysmal burg of strip malls and chain restaurants.
The animation style is unlike anything you have seen before: photos of the actors are taken and treated with a photoshop filter, the background are drawn, and the food is photorealistic. Some things are completely live action though, like Jefferton's Married News Team. Oh and like every episode has some special guest: Tenacious D, David Cross, Sarah Silverman, Brian Poesehn, Zack Galiafinakis, John C. Riley... It's a surreal absurdist comedic entity of geniosity that may never be matched again. The complete Adult Swim-run series is on 3 DVDs, and every episode has commentary and tons of bonus stuff. I cannot recommend this more highly if you are in to "indie" comedy. It's that amazing.
P.S. - The creative team behind Tom has a show currently on Adult Swim - Tim and Eric Awesome Show Great Job that is also very very good.