My current motor home is on a E450 and when I hit a bump I know it. I came from a tcer with a 2500 carrying it and it drove like a car.
That being said I would rather have the 450 for the engine and other heavier parts for the long haul. The stiffer drive is only noticed once in a while but when I can go up a hill with all the other traffic or be able to pull more then I figure the roughness is worth it.