I actually like this idea. Something along the lines of the GBA/DS Mario RPGs where some unusual outside source is threatening the Mushroom Kingdom. Somehow Bowser ends up discovering how to destory the menace and goes out on an adventure. Along the way, Mario and Luigi are trying to solve the problem too, but they see Bowser as evil and keep on getting in his way and stopping him.
Towards the end, the Mario Brothers end up making everything worse, and Bowser last minute has to save the day.
But how do you make the experience different? I say turn it into a blend of the Platform RPG that defines the Mario RPGs, and more turn based strategy like the Advance Wars and Fire Emblem series.