FWIW, I've countered my E450's rear differential ratio slightly by increasing the diameter of the tires, which gave me about 0.6 inches more ground clearance for off-highway desert use. I would have went even larger on tire diameter except for the DW not wanting to climb too much higher up into the cab. We still get great slow speed and steep slope crawling with minimum tranny slippage and heating, however, so I've not completely negated the E450's lower rear differential ratio.
The fender wells and suspension could even take a lot taller tires. One Class C owner in these forums went up to 235/75R16 Load Range E tires all around, which netted him great ground clearance plus a much better weight carrying margin with these tires even though they were still rated as Load Range E. Apparently what a given Load Range rating provides goes up in lbs. with larger tires even though they still carry the same Load Range designation. This was news to me until I researched it before putting on new tires a couple of years ago.
I'll do some more research on my own to nail down E350/E450 chassis differences for Ford's latest model year. If the differences are indeed less than when we bought our Class C - then it's even better that we went with the heavier duty chassis back then.
I give a lot of importance to a seemingly minor difference - the E450's thicker frame. This helps to keep the coach floor on a constant plane when traversing rutted roads because front-to-back frame twist will be less due to it's added strength under any given coach weight it's supporing. Front-to-back torsion forces on a standard Class C coach's structure are a no-no.