They turned The Powerpuff Girls into Powerpuff Girls Z, and I think it lost some of its edginess. But if I had to list a few possible choices...
Clone High - A romantic comedy about clones of famous historical figures in high school. Hell, with so many animes taking place in high school as it is, adding in a few clones plus a robot vice-principle is hardly a stretch. It practically writes itself.
Galaxy High - Two earth kids are invited to attend high school in outer space where all their classmates are freaky aliens. It's a fish-out-of-water mixed in with some romance. Toss in a shadowy school board out to enslave the universe and you've got a hit. Plenty of opportunities for alien fan-service, too.
Two Stupid Dogs - This one I'd change a bit and turn it into an (even more) absurdest comedy about two dogs who teach at a Japanese high school for girls. No plot or point to this one. It's just two very stupid dogs teaching high school and the wacky adventures they have with their students. There will be a cultural festival episode, a hot springs episode, a spooky ghost story episode, cooking episode, etc... "Isn't that kawaii...BUT IT'S WRONG!"