For the original question.
The 1st thing is full sized trucks & SUV's, in the forseeable future, will never get great MPG. So, people that are really worried about fuel economy should sell the truck and go buy a car. Now I am one such person who is extremely anal about MPG. I fret over it like you wouldn't believe. Unfortunately due to my line of work( carpenter and cabinet maker )I need a truck. Also, the only thing I do for enjoyment is waterfowl hunt and that means towing my duck boat during the winter months. I need a truck and it needs to be 4X4. So, I have become obssesed with optimizing MPG out of my trucks. Here is what I have found to date and it seems to basically be the same results regardless of MFG...
Things that should help:
1 - Tonneau cover. Soft tonneaus or lightweight hard tonneaus such as the Undercover will help MPG some. Not huge gains but some. Upwards of approx 1 MPG on some rides although I have never seen that much. Maybe .5 MPG.( NOTE - If you go with a heavy hard tonneau like a full fiberglass one or a roll top one that adds a couple hundred pounds you lose any MPG gains because of the extra weight - Just about a wash )
2 - Proper Maintenance. Keep up with your scheduled maintenance. Keep your oil & filter changed regularly, don't wait 100K for a new set of plugs - check every 20-30K or so and replace as needed, keep an eye on the air filter and change it frequently( 10K or less ), if equipped change the fuel filter routinely, keep all fluids topped off to their proper levels, and so on. Run some quality fuel injector cleaner through every 3-5K as well. Keep on top of your maintenance and the engine will run more efficiently and will use less gas.
3 - Keep an eye on your tire air pressure. Properly inflated tires actually will help MPG while underinflated tires will hurt it. Putting the max PSI a tire is rated for in will give the best MPG( that PSI in tires can )but it leads to faster tread wear. So, go with the recommended PSI and check it regularly. Not only will it help keep MPG in the optimum range but soft tires, like over inflated ones, wear quicker so it will help lengthen your tread life.
4 - Swap to synthetics. If you swap your oil, tranny fluid, axles fluid and t-case fluid over to full synthetic you will greatly improve the efficiency of your drivetrain and thus improve MPG. There is a significant reduction in friction with synthetic fluid vs conventional fluids and thus your drivetrain components will work easier. It will require less pedal to get the vehicle going and thus less gas will be used. You "might" see as much as a 2 MPG gain doing this. Usuually around 1 MPG. You also reap the benefits of extended service life on the areas synthetic is used because of their superior properties vs conventional oil.
5 - SLOW DOWN & GO EASY ON THE THROTTLE! This may be the biggest one of all. Don't hammer it to the floor when leaving every stop sign or traffic light. Accelerate modestly and don't worry about always being the 1st person to the next light. When on the highway instead of going 80-90MPH slow down and go the speed limit. Not only will you help your MPG drastically but you will be safer. Keep it at or under 70 MPH. Especially if you are running high 3 and low 4 range axle ratios. Try and keep RPM's UNDER 2000 for optimal fuel economy. In my truck( 05 EC 5.3L 4X4 265-17's & 3.42's )I set cruise at approx 62( yes even if 65 zone - I just stay to the right out of the lead footed folks way )and my RPM's are right around 1600-1700 or so. I see 23 higway doing that. If I jump it too 65-70 MPH the RPM's creep to 2000+ and my MPG plummets rapidly. I see maybe 19 MPG at best if I go 70-75 MPH and up to 23 if I keep it under 65. That is a HUGE difference. I think the biggest factor that determines people's MPG is their driving habits. Those with the heaviest throttle foot get the worst MPG. Slow down and accelerate easy and your MPG "WILL" improve. You know, there is a reason why 55 was set as the national speed limit during the last oil crisis. That is because it has been proven to provide the optimum MPG for most vehicles.
6 - Add electric fans and/or under drive pulleys. These two mod's help to decrease parasitic accessory drag on the engine allowing it to make more useable power which means better MPG. You don't have to use as much gas to get going and stay there. Same principle as synthetics. If you are always hammering the throttle though it doesn't do much.
7 - If warranty is not a concern to you having a custom tuner optimize your PCM for fuel economy can help. Handhelds will a little I guess but the custom tunes will provide the greatest gains.
8 - Remove all unnecessary junk from your vehicle. People are usually amazed once they how out their ride at all the crap they have in there. Extra weight means extra to haul and extra gas is needed to do so.
Things that don't work:
1 - Stay away from gimmicks like the Tornado Fuel Saver, fuel economy pills( yes they actually have these ), and things like throttle body spacers. They don't work and are just a waste of your money. Even time tested and proven add ons like CAI's and exhaust upgrades don't work as well on modern vehicles as they once did. Every single thing is controlled by the computer these days and when you start changing things the factory computer just can't adjust properly and generally MPG suffers. For every 1 guy who claims his CAI or exhaust helped his MPG 10 others say it did nothing or hurt MPG.
2 - Avoid cooler t-stats and the like that significantly lower engine temp. That used to be a great way to boost power and MPG on older vehicles but on today's vehicles they are designed to run hot. Until they reach the proper operating temp they run rich. So, if the factory wants them to run 195-200, and you throw a 160 or 180 t-stat in, your truck will always run rich and thus get worse MPG. That can also lead to other problems down the road such a fouled O2 sensors, excessive carbon build up, and the like. Unless you have done a ton of mod's that require a cooler t-stat then keep the factory heat range.
3 - Stick with the factory oil viscosity. Like with the t-stat temp range issue todays engines are designed to run on water like oil. 5W-30 and 5W-20 are where it is at these days. Avoid 40 and 50 weight oils. Not only are they harder on the internals, as the oil system is not designed to handle them, but they will reduce MPG. Not a lot but some and this thread is about optimizing economy. So, stick with what the mfg wants for viscosity.
Bottom line there is no bolt on or pour in magical part that will drastically improve your MPG. All you can really do is slow down and keep your vehicle in top shape and THAT will optimize your fuel economy. There are a few things like tonneau covers that can help out but they generally are not huge gains and the cost means doing it for fuel economy alone generally is not worth it. You would need to drive 200K to make up what you spent on the part in question to break even.