I saw a 1 mpg improvement on about 300 miles of 50-55 mph. This was with home-made desplined caps.
My truck is a bobbed deuce and I burn WMO fuel. I purchased and de-splined a set of hubs a while back. I also installed bronze bushings (found them on ebay) and grease fittings in the caps. De-splining the hubs serves to reduce the drag of the tires in turns caused by the ackerman angle built into the steering geometry of every vehicle on the road. I picked up about the same gain in MPG, 1 mpg, and maybe just a little more. The best gain for me was a somewhat reduced steering effort. I think the turning circle got a bit tighter due to the reduced drag but I never bothered to measure it. I have a set of hubs with the splines still in them. If I need 4X4, I just swap them out.
Your best bet for efficiency would be to have your injectors pulled and make sure they are with in specs.
Plus One. The Deuce ain't never gonna be a MPG champ, but there are incremental gains to be had by: 1) having your injectors pop-tested and balanced, 2) removing that 10 pound radiator fan and replacing it with either electrics or a plastic flex fan, 3) de-splining the front hubs or installing lock out hubs and 4) installing better tires. Almost ANY tires will give better mpg's (and wear) than the NDT's. Like the loose change in your couch cushions, it does add up.
Information on the plastic flex-fan can be found here:
http://www.steelsoldiers.com/showthread.php?119295-Nylon-Radiator-Fan/page4&highlight=flex+fan
If you are burning WMO fuels, pay careful attention to the viscosity of your fuel blend. If you blend WMO fuels carefully, you can get fuel mileage pretty close to that of diesel.
There may be some aerodynamic gain to be had by reducing the frontal area of the truck. I am thinking this may be done by lowering the height of the bed cover to even with or maybe a little lower than the roof of the cab.
An air dam running left to right under the front bumper might also help reduce turbulence under the truck and reduce aerodynamic drag. This may also serve to increase the speed of air through the radiator and help out with cooling. I haven't tried these last two yet, but they are on my list.
Anything that reduces rolling resistance, aerodynamic drag (frontal area), or parasitic drag on the engine will help out with MPG's, if only a little. Is it worth the cost or the effort? I guess that's up to you.
Like everything else, there are two schools of thought on these ideas and both sides are pretty passionate about their pet theory.