I just returned from an 18 day/2,500 mile trip through the southern Rockies in our 24' Class C, E-350 V-10. The V-10 is a beast that ate up the 10, 11 and even 12,000'+ passes with out even breaking a sweat. We were pulling a small trailer with my motorcycle on it (hit the Cat scale on the way home and it is 960#), and running right at our GVWR as I carry lots of tools, toys etc..
Yes, naturally aspirated gas engines lose roughly 3% for every 1,000' of elevation but as elevation rises air density decreases which = wind resistance reduction. Based on the consistent mileage and performance we enjoyed throughout the trip I suspect these two factors are close to zeroing each other out.
Rarely did the coach shift below 4th gear and was very happy on most grades at 3,250 (Max Torque of 420#), though we cruised at 2,000 - 2,200 to maintain 60 mph on most of the highways. Occasionally it would drop into third and rev to 4,000 - 4,500 for brief periods but the shifts, both up and down were smooth and predictable.
As we have for the last 2 years and 25,000+ miles we averaged 9.5 (including some generator time), for the entire trip. In Colorado our daily average was closer to 9. Our worst mileage was 8.8 and the best 10.3. Sprinters have their charms but towing is not one of them and a 4,000# trailer, which will probably only get heavier over time, is going to be a tall order for a Sprinter in Colorado. That much trailer calls for a V-8 or V-10.
As always.... Opinions and YMMV.
:C