A comparable (same year or two), E-350 will ride much smoother than an E-450. The 450 will be 2 to 3,000# heavier and consequently will have a stiffer suspension (though loading them heavy is reputed to smooth the ride out somewhat). The 450 will have a 4:56 rear end vs the 350's 4:10 assuring significantly worse mileage (especially when loaded/towing heavy).
Don't get me wrong, I think the 450 is one hell of a chassis and if you actually need that much truck it is definitely the way to go. If however your Class C is 25' or less the 450 will be more than needed. Over 25' the 450 becomes the better choice.
The 450 does a decent job humping up to 32'+ Class C's but, it has the exact same motor and transmission, 6.8L 305 HP (at 4,250 rpm - 420# of torque at 3,250 rpm), V-10 mated to the excellent 5 speed Torque Shift trans, found in a late model 350. Hmmm, in which one will you get up and down the mountains more efficiently?
Candor alert: Yep, I have an E-350 in our 24' Nexus Class C. After nearly 2 years and 23,000+ miles I could not be happier with the performance of our motorhome. I just started towing a 9' motorcycle trailer to carry my BMW R80 RT, bike and trailer weigh in at a paltry 850#. Can't even see it in the mirrors and the V-10 sure doesn't seem to notice.
I thoroughly enjoy having the smoother ride and better mileage that we get with the E-350. We bought used but given a choice (350 vs 450), I would have stayed with the 350. We lucked out in that the original owners opted for the 55 gallon fuel tank as many 350's come with just 40 which is less than ideal.
If you are going to load light and tow next to nothing you can get by with the Mercedes chassis but 188 HP and 320# of torque can only do so much. The ride will probably be smoother (if you can ignore the atrocious Mercedes seats), but you will be giving up half or more of the payload/storage of a Ford (or Chevy). It all comes down to how you are going to use the rig.
As always.... Opinions and YMMV.