get a set of afr 165's, do a mild hydraulic roller cam setup and run about 10:1 cmopression. the more compression you can run the better the mileage will be in general. also do some imternal engine coatings to reduce friction and the coatings for the piston face and the combustion chamber of the heads to hold the heat in the chamber. this will also help the engine run a bit cooler as well.
next install the above mentioned aod or t5 and a decent set of gears in the 3.25 to 3.55 range. anything lower like 4.11's will kill your mileage on the highway but a higher gear such as 3.00 or 2.79 will kill your low end power making the engine have to work harder around town.
you should also consider a conversion to fuel injection as well. there are a ton of choices, stock 5.0 efi system, mass-flo, edelbrock, holley pro-jection, etc.
personally i would go with either the stock style 5.0 system or the holey pro-jection if you want to retain a more stock looking engine compartment. the holley commander 950 digital system is what i plan on putting in my car when the time comes.
the only other big thing i would recommend is to run as tall a tire as you can as well, since that reduces the revolutions per mile a lot.