Well, I am going to use the 1999 Ram 2500 as a benchmark. 13.8 mpg unloaded.

Here's what I spec'ed for a friend's '75 440 powered 4x4 truck. He was getting between 6 and 8mpg unloaded.
KB184 pistons.
Hughes HE1423 camshaft.
Edelbrock Performer
Can't remember carb.
Headers and 2 1/2" duals
MP high perf electronic ignition kit.
Stock 452 heads with fresh valve grind.
The machinist had to work to get the squish right and the compression right, finally left the door at about 9.5:1.

Mileage immediately improved to a hair over 15 mpg. The truck looked better, drove better, sounded better, hauled better, and just generally was better.

If you think about headers in terms of flow, then they don't help. The longer tubes of the headers keep the exhaust pulses separated and exert some sort of a ram tuning effect, that's why they are used.

R.