I really like the idea of a small motor home being built on an over-capable E450 chassis, but for reasons most people would not consider.
We would all agree the E450 chassis is designed to manage a much larger motor home than a tiny 22 footer like a
(Phoenix Cruiser 2100) with a short 138" wheel base. The suspension is so very stiff on such a rig that it must be terribly rough on the house and contents, and also the occupants.
But.......
For a little extra money, you can take such an over-capable rig to a truck suspension shop to remove the appropriate quantity of rear leaf springs, and replace the front coils springs to softer ones
(Like I Did With My Rig Here). The end result is that you have over-rated brakes along with other over-rated safety and durability benefits like a thicker main frame that will take longer to degrade from rust. I imagine the thicker E450 frame would also decrease potential body flexing (if any).
I understand that the difference in fuel economy between the E350 and E450 in past years is no longer applicable. The rear differential gear ratio is the same used in both for a few years now because the additional gears in the latest transmission compensates appropriately.