I've got the 5.4. I did the lift, 285's and added a roof rack pretty much all at once... and I didn't do anything to adjust the speedo/odo - I stayed with stock 3.73 gears. My "mileage" dropped from 15mpg fully loaded highway to 10-11 fully loaded highway. I'm sure a couple of these mpgs are due to the inaccuracy of the odo (and someone smarter than me could calculate it, I bet), but I definitely lost 1-2 mpg I'd bet. I just got the van back from the shop this afternoon after switching to 4.10, so I should have better numbers in the future. I have not noticed a significant problem with 3.73s, other than the speedo/odo, but there was a bit of a dip in performance (minor) - it could be the tires or the gears. Again, I'll see how it changes with the new R&P.
Addendum:
There is a very noticeable improvement in performance with the new gears. Feels smoother and is particularly noticeable going up steeper hills. I expected some improvement, but it is much more than I thought - at least at the lower speeds/street driving. Note, this is not a huge performance increase, like upgrading to V10/5R110, but a nice noticeable improvement. I'm still breaking in the gears, so I'm still babying it and nothing over 60mph yet. I'll update once I get a few hundred more miles on it... and I'll get a better mpg avg.
2nd Addendum:
2500 mile road trip last month. Fuel economy averaged about 12mpg - best was 13.5, worst was 9 (85mph on I70 into a head wind). All fully loaded with gear, people and a pile of bikes on the rear rack.
The new gears were a small, but clearly noticeable improvement in lower speed performance and shifting. It was less notable at moderate highway speeds (70) and slightly decreased top end as I approached 80mph (I don't get up there very often, though). Overall, a good investment.
Handling was still great on the trip.. very comfortable one hand driving at 80mph.