My 2015 GX460 is running Toyo AT3 35x11.50 on 0" offset, 4.88s, 3" Toytec Aluma 2.5 F/R, BMC, PCK, SPC upper, KDSS spacers, sliders, rear e-locker, 1" body lift, rear airbags. I live in Denver, and I tow a 4k lb (wet) camping trailer.
I never drove the truck with the 35s without the 4.88s, but I can not imagine it being a good experience at altitude while towing or even general driving. With the 4.88s, I can maintain traffic speed on all pass climbs with the trailer, but that's it. Stock gearing would be putting ~25% less torque to the ground, so I doubt I'd be able to break 35/40 mph on the up hills without the gears and AT would get even hotter.
I tried running the truck without the 1" BL, and there were rub issues in front and rear mud flaps. When BL went on, removed rear mud flaps, cut out room around the washer fluid reservoir in front, that solved all rub and the truck now fully stuffs without rub.
Only thing I would change is the Aluma 2.5, I think they run a bit firm, not like 1-ton without load harsh, but a sports car. I don't have any extra armor/weight, maybe these were spec'd for a fully armored truck. Cornering is flat, is as easy to drive as stock. Gears make a bit of noise, but not intrusive, and I can't hear the Toyos, only the gears.
Future plans include OEM (or similar) tranny cooler. On long climbs, if truck is in 3rd and no TC lockup, TC temps will hit 260+ on long climb, and it's tripped the 3rd gear TC lockup override before (I don't want to make this a regular occurrence). AT temp has been high 230s. Extra cooler won't stop the heat soak, but will slow it down. If you did this without gears, I think you'd get really hot really quick.
And finally, I used to tow a 5k lbs trailer with huge frontal area, and that was not great, I feel like 4k lbs, lower profile trailer is limit for me.
EDIT: MPGs are same as stock. 12/13 around town (I have lots of short <4 mile commutes, this kills MPG). 19/20 on highway (I don't run a rack or RTT). Towing 4k trailer, 9.5 mpg round trip with lots of climbs. 5k trailer was something insane like 7.5mpg round trip.