Hi Steve,
This is the way I see it.
Attractions of the Mercedes Sprinter.
1) better fuel economy with the diesel engine
2) nicer ride and driving experience along with better ergonomics
3) taller cab area for easier entry to and from the house
4) it's a Mercedes
Attractions of the Ford E350.
1) significantly lower purchase price
2) lower maintenance & gas prices combined, balances the lower fuel economy
3) more capable chassis carries much more weight and tows better
4) the V10 gasoline engine with 50% more power & torque performs better
5) the engine can endless-idle for alternative heat, a/c, & battery charging
6) over-head bunk is lower offering more bunk headroom and easier access
7) many more places to find service, especially important in remote areas
I feel getting a Sprinter is favorable if you are putting on piles-of-miles per year. One example would be if you chase ball teams all year long.
We own a 2007 E350-V10 motor home, bought brand new. I tracked fuel consumption for many years. From home near Chicago to destinations out west, I consistently averaged 9.2 - 9.5 towing a Jeep Liberty all the time, and 10.5 on the one trip out west towing nothing. Calculations was for the entire trip average without consideration to the fuel we burned running the generator. So the "true" mpg would be better.
Keep in-mind that most Sprinters are equipped with a propane generator because it is much cheaper and weighs less than a diesel generator.
When shopping for a "used" motor home, the E350 and Sprinter seem to be priced the same. The extra cost for a Sprinter seems to greatly diminish in the "used" market. That is great news when buying a used Sprinter, but bad news if you are selling the Sprinter you bought new.
Ron Dittmer