Sorry. Got carried away. Better fuel efficiency is something we all want...but it's a full time 4wd 5,000lb beast we are talking about (with no air dam to boot).
As mentioned, smaller contact-patch tires that are more lightweight (and have smaller voids between knobs) will help, especially when properly inflated. I think going a little over the recommended inflation is also good for mileage if your 80 is almost always on road. You can always air down for off road duty. Making sure your tire pressure is correct regularly is huge (I'm sure you've seen the numbers on how much gasoline we could save daily in the US if everyone drove their vehicles with properly inflated tires).
Other things that can make a difference:
Full engine tune up
Cold air intake
Regular oil changes
Get the truck aligned if there are any questions as to the current alignment
Driving style - smooth it out, slow it down. I also make a point of taking the route with the least number of start/stops (ie- take the interstate instead of going through town)
My guess is there is some efficiency to be gained in the exhaust system as well but I have no idea (beyond the fact that a Subaru I owned a while back had a defective catalytic converter and it was costing me 4mpg - once Subaru was able to identify the problem, which took them 20,000 miles from when I first noticed, they replaced my entire exhaust under warranty).
I religiously reset my trip meter with every fill-up so I know exactly how many miles I am getting per tank and always do the math when at the pump to check mileage. This is a good practice because if your mileage worsens, you know right away and can start figuring out what happened.
I'm sure there are some other tricks but these will definitely help you make sure you are doing everything you can.
Drive as close to 2000 rpm to maximize fuel mileage. It's a radical but proven idea - less throttle = less fuel burned. If I run on cruise at 65 I usually get over 14 mpg; 75 - 80 will drop towards 11 mpg. I just have to decide the time vs money argument for that day... I also run without the roof rack most of the time. Lately it seems the spike in gas prices has made running at 65 more agreeable, I notice many more 18 wheelers are going slower these days as well.