Here is my experience:
I bought my 84 K5 with 6.2L Diesel, 700R4, NP208, 3.42:1, 31" 'buckshot mudders' All factory.
I added an ATS Turbo and had the transmission rebuilt (supposedly built up too). All was fine, I was getting up to 24 MPG on the highway.
Changed to 33" Dueler MTs, began to feel doggy. Eventually the transmission took a dump, prety sure it was a poor rebuild. From what i determined, the torque converter is what failed and ruined the rest of the transmission. Put in a well built 700R4 and was about the same. Then i regeared to 4.11:1, made a huge difference, transmission temps are now alot cooler and highway speeds are still around 75mph. Gearing seems useable even with my 35x15.50 TSL SX but i wouldnt want to go any taller without regearing. I was given an early 80s 1 ton single rear wheel with a SM465/NP205/D60/14FF combo that has 4.56:1 gears and are about to be transplanted.
My main concern would be for the auto transmission, especially if it is a 350 or a 700R4. Dont skimp on the torque converter. I would also put a electric fan on the trans cooler to keep air flow through it while at crawling speeds.