I have never seen a performance wire set improve economy over stock wires, though they are useful in high RPM applications.
Yes, a bed cover should help, and also removing the tailgate, or useing a slotted tailgate should help a little at freeway speeds.
Also, if you have the luxury of breaking a new engine in, to help insure it gets the best power and economy it can, run it hard for the first 20 mins or so, with lots of hard acceleration and deceleration. It does make a difference, especcially 100,000 plus miles down the road, really helps the engines last longer. A hard break in must be performed with the engine warmed up, and once arm, it should be done immediatly, rather than a few easy runs first. If there are close tolerances, or burs or other problems with the engine, no amount of easy running will fix it, and I'd rather have it cause a failure sooner rather than later.