Hi,
I replaced the original 3.9 diff in my 56 with a 3.38 a couple of years back. Pickup has the original 4 speed and 235. The gearing change helped a lot for freeway driving, but it doesn't climb hills nearly as well. 65 on the freeway is comfortable. I wouldn't go much faster than that. I still stay in the right lane and keep plenty of distance from the guy in front.
Other changes I considered mandatory were 3pt shoulder belts, tapered roller wheel bearings, new kingpins and tie rod ends, all new brakes with dual master cylinder.
I added sound deadening and insulation too, which obviously doesnt do anything for the engine but helps from the driver's perspective. Another simple tip that someone else mentioned is to make sure your valve clearances are set correctly - makes a heck of a clatter at freeway speeds otherwise.
Finally, make absolutely sure your brakes are adjusted evenly so you stop straight in a panic situation.
Hope this helps answer the OP's question.
