If you end up with an E-350, which is the way to go in a class C at 25' or less, you will get a 4:10 rear end. Any model 2008 {I think}, or later will have the 5 speed Torque shift transmission - the 2016/17's have the six speed.
An E-450 in a 25' or less class C is overkill and you will inherit a stiffer ride and worse mileage vs the E-350. Keep in mind you will be running the exact same V-10 and trans. I love our E-350, 24' Class C with the V -10 and 5 speed Torque Shift trans married to the 4:10 rear axle {vs the 4:56 in the E-450}.
If you plan on towing heavy, more than 3,000#, then the E-450 might be a better choice but as noted you will give up ride quality and mileage.
With any V-10 the worst thing {as in least efficient}, you can do is to baby it. Put your foot down and go. You can run a V-10 at 5,000 rpm all day and never hurt it but since max torque comes at 3,250 and max HP at 4,250 it is not likely you will ever need to.
"The good thing about the E-series chassis, is you can lock out overdrive."
You should be running with Tow Haul engaged {or overdrive locked out, basically the same effect}, anytime you are towing or are running anywhere near your GVWR. This locks up the torque converter eliminating any slippage/friction and keeps your trans temps down where they belong. On long down hills {think 8 to 10 mile 6+ per cent grades}, you will be able to descend without touching your brakes or burning a drop of fuel. So what's not to love about using TH?
As always .... Opinions and YMMV
:C