Back in the days when William Shatner was in the classic Star Trek, he would have made a good Chief Wiggum. Adam Sandler is the 'Comic Book Guy' right?
It would be cool if there was a simpsons movie, doesn't mean there can't be anymore cartoons though
Wasn't there a line in one of the episodes where someoone joked that John Goodman is going to play Homer in a movie?
Anyway, use the actual Harry Shearer to play Kent Brockman...and maybe disguise him for some other parts...(maybe even do that in some instances with some of the actual voice actors..) Lisa Simpson...use the actual Yeardley Smith.
Professor Frink...Jim Carey (or maybe Flanders)
Sideshow Bob...use the actual Kelsey Grammer
Moe...Rob Schneider
Bumblebee Man...Horatio Sanz (from Saturday Night Live)
Additionally, how about just putting Dan Castellaneta in a rubber/fat suit to play Homer? (If they can turn a non-obese Eddie Murphy into the fat Nutty Professor, then why not?) Who better to play Homer than him? And have Julie Kavner play Marge.
They both already have experience as screen actors.
Conceivably, there is a way, (by use of computer graphics), to put a "digital costume" on all the actual voice actors from the show...but what would be the point? It would basically be the same as the hand drawn tv show, but with better graphics.
I say use some of the original actors in key parts; like I mentioned, Homer, Marge, Lisa, Kent Brockman...