People and machines are not the same. A truck is not going to tire out if it carries a particular weight once or 100 times, assuming the truck isn't overheating or otherwise bending at the frame/suspension components.
The 3.92 only offers the engine a slight mechanical advantage (again, between 0 and 24mph). That 3.92 is not going to make the frame or suspension stronger. It's not going to stop you faster if you have to jam on the brakes. It's not going to save you if a gust of wind hits the side of your trailer. It's not going to balance your load or prevent sway. It gives you a bit better acceleration and maybe a little better at engine braking, too. That 3.92's mechanical advantage WILL certainly help your truck handle a pulling load up and down steep grades, or if you're REALLY pulling a load on a flat surface (like 30,000lbs), it might mean the difference between you actually getting up to a usable speed, at all.
I'm sure people are familiar with the Ford 1,000,000lb pulling stunt:
Pulling 1-million lbs is easier than it looks, I'm sure our trucks could do it too. The problem is it's not practical at any usable speed or on any grade. It's no longer a question of which axle ratio you have.
Bottom line, my truck (with the 3.92) is rated for 9,900lbs of towing capacity, my truck (with the 3.21) is rated for about 8,200lbs of towing capacity. Same exact truck in every single way, same brakes, frame, engine, suspension, hitch, tow assists, etc. In my opinion, I'm probably not going to tow more than 5,000lbs except once in a blue moon...BUT, if I felt like putting 9,900lbs on the back and hitting the highway, I'd probably be comfortable with that, unless I was planning to climb steep hills. In fact, I'd probably be comfortable pulling 15,000lbs at mild speeds and favorable conditions, so long I'm not overloading the GAWR.
In fact, the GAWR and 2X the Tow Rating are the only numbers that I feel are the "Hard Limit" on what what our trucks could do, REGARDLESS of speeds or external road conditions, like even 1000ft up my neighborhood street.