My first 59 gmc 1/2 ton shortbed had a 6 cylinder, 3 speed and 3.08 gears from the factory and 29 inch tires. No problem starting in 1st or second. Not so good at towing a trailor. Typically got 14-16 mpg with the original carb, and 12-14 mpg with a 4bbl holley. Truck weighed around 3500 lbs empty.

I had put the 3.38 gears in my current 59 gmc with pontiac v8 and overdrive transmission. The gears did ok with the 336 gmc engine, but the rearend did not survive the engine swap to a 59 pontiac 389 bored and stroked to 447 with 3 deuces. The rearend housing was torn apart.

I have since replaced the HO33 housing with a 9 inch, and changed the gears a couple of times. My gears now are lower than stock, but I still cruise 70 mph at 2500 rpm because of the OD. I may change the gears to around 4.10 for a little more economy. However the 4.30 gears I have now are real responsive with the 31 inch tall tires.

As far as mileage, here is how my 59 1/2 ton longbed did with various engine/tire,transmission combos. The truck weighs a touch over 4000 lbs empty, and with the spare gas and tools I carry, it tips the scale around 4400 lbs.

10 mpg with 336 v8 motor, 28 inch tires, 3.90 gears
12-13 mpg with 336 v8 motor, 28 inch tires, 3.38 gears with 27% OD transmission
13-14 mpg with new 447 inch pontiac motor, 28 inch tires, 3.70 gears, and OD transmission
14-15 mpg with 447 motor, 31 inch tires, 3.70 gears and OD transmission.
10-12 mpg with 447 motor, 31 inch tires, 4.30 gears and OD transmission

The transmission is a NV4500 5 speed adapted from a dodge 1 ton diesel pickup. There was a 4 speed sm420 in my truck when I purchase it.

The truck responded great with the 3.70 gears and the 28 inch tires. There was a noticeable loss of gearing when going to the 31 inch tires. Acceleration was poor in every gear. 4.11 gears with 31 inch tires should respond the same way as 3.70 gears with 28 inch tires. I ended up moving on to 4.30 gears for even better acceleration, however the loss in economy is killing me. I may switch to 4.0 to 4.11 gears for more economy.

With OD, you can have the low gears for acceleration, and still cruise at a respectable rpm.

The OD effectively gives you a highway rear end gearing. The NV4500 has a 0.73 5th gear for 27% OD

3.90 gears effectively become 2.85 gears in OD
3.70 gears effectively become 2.70 gears in OD
4.11 gears effectively become 3.0 gears in OD
4.30 gears effectively become 3.15 gears in OD
4.56 gears effectively become 3.33 gears in OD
5.14 gears effectively become 3.75 gears in OD

Anyway tire size, gears, and transmissions can be mixed and matched to give the desired performace. The OD transmissions give you the ability to have acceleration and economy. However you generally have to choose between the acceleration performance and the economy. You can have 1 or the other but not both. Some combos work better than others, but in the end, everything is a compromise.