A little late here (not around much)...
I have the V-10 in my 2010. Weighs about 8400 lbs. Not an ideal motor IMO. I call it a circle track motor because you have to rev it out like a race motor. Torque is at about 3500 rpm's which is ridiculous for a big block.
I started with 4.10's in my van on 285/70-17 (about 32.8"). Did ok but 4.56 would of been better.
I now have 295/70-17 (about 33.3"). 4.10's would downshift on a flat freeway going over an overpass. Yuk Out of its ideal power zone.
Went to 4.56 gears. Much better, but I feel 4.88's would be better. As we know the V-10 wants to spin. And you will never get any sort of mpg's with a V-10, it just ain't going to happen. I've towed a 4500 lb dry travel trailer. Now, big flatbed & enclosed trailers weighing 2700 empty & about 6500 loaded (so apprx 14,500 combined weight).
I am turning about 2250 rpms approaching 70 mph. I think I should turn more like 2500 at that speed. Its not going to hurt your mpg's because your mpg's will always suck. Over gear on ratio if you tow a lot IMO.
My rig has a intake, aftermarket muffler and a 5 star tune. The 5 Star tune did give me more power. We (5 Star) have estimated maybe a 75 HP gain. But it hurt mpg's. I used to be able to get 10-11 mpg's sometimes lol, but with the 5 Star tune its 8-10 mpg. Yes shift points are better (a whole nother story).
So... build up your V-10 for power. Forget about mpg's.
Or find a diesel Econoline. A 6.0 diesel will out power my V-10 anytime.
Oh, I bought a Duramax diesel Chevy truck for towing and it kicks butt. No need to tow anything sizable with the van anymore. Ahhh. Diesel power!