The best single mod really comes down to your rig, driving style and what type of off roading you do.
If you have a rig (i.e. Chevy Blazer) with enough power and an automatic transmission gears are not as important because the torque converter helps out a lot. A rear locker would be an excellent choice for a single best mod.
If you drive a Toyota with a standard transmission a rear locker would be an excellent mod for dirt/mud type trails where some speed is required, but if you're planning to run technical trails that require slow control you can't beat 4.70 transfer case gears for the ultimate control.
I drove my 85 trunk in Moab with nothing more than a mild lift and 33 inch tires. I ran many of the difficult trails, but was constantly stalling because it simply wasn't possible to keep it running going the speeds that were required.