I did a major service to my 22 F150 a few months ago when I was at 60k miles. Did the front and rear differentials, transfer case, and transmission drain and fill with a new filter. I'd replace the driveline fluids and not do any fuel system cleaning, I'm a fan of replacing oils more often than needed. The diffs and T case are easy to do yourself, the transmission is a PITA.
The differentials were pretty easy, the rear one I just unbolted the pumpkin to drain, used a Lubelocker gasket (so no RTV) and filled with new gear oil. I also replaced the OEM cover with a Spicer one to get a drain plug, but that's not necessary. Front one I used a hand transfer pump to pump out the old gear oil from the fill hole and refilled. Transfer case is just 2 bolts to drain and fill the ATF, takes like 10 mins.
My truck has the 10R80, not the 10R80 MHT so yours might be different but it was not a fun job. To pull the dipstick, you have to fish your hand next to the catalytic converter to pull it out of the top of the transmission. To properly check the level, the trans has to be hot so I burned my hand a couple times. Basically I used a hand pump to suck as much ATF out of the dipstick hole as I could, dropped the pan and replaced filter. Bolted everything back and refilled through the dipstick. Each power train has a different cooler setup, so on my 5.0 I was able to drop the pan without having to move any cooler lines, but I know on other engines you may have to disconnect exhaust pieces or cooler lines etc to gain access. Drove it around to get it hot then check and adjust the level. If you're not mechanically inclined, I would highly recommend paying someone to do that job for you.
