Make a sequel to Bowser's Inside Story. Problem solved.

Super bowser bros maybe. But what would he be taking out, the same mushrooms that serve him? or toadstools? At least in the new mario party you play as boswer: the party crasher

On mario party 10 can be a protagonist.:P

its long overdue

I could see it working in a Dungeon Keeper style game.

You get to set up peaches castle and fill it with traps and enemies and such to try and defeat Mario. It'd work well with the gamepad, too.

That would be pretty awesome, but who would be the main villan? Mario?

No, there is a reason that Bowser is only playable in party games (Smash Bros, Mario Kart, Mario sports, etc) and RPGs (M&L: Bowser's Inside Story and the original Super Mario RPG), unless you are going for a koopa civil war story, you would have to create a whole fleet of unrecognizable new enemies.

What if it was Bowser vs Wario vs Wart?
Each villain would have its own set of worlds, enemies and special ending.