When we got the F450 with the 4.30:1 rear axle, we fully expected worse fuel mileage than our F350 with the 3.55:1 rear axle. But that wasn't the case at all and that's likely due to the 10-speed transmission in the F450 (the F350 had a 6-speed).
Towing at around 65MPH, BOTH trucks are getting around 8.5MPG towing which was a pleasant surprise! Around town driving (not towing), we're actually seeing BETTER MPG on the F450 at around 17-18MPG! The F350 would get 16-17MPG.
We've only had the F450 for a month, and I need to manually verify what the computer is telling me, but it was pretty accurate on the F350.