I'll toss in my 3 cents worth.
I have an 89 GMC K1500 4x4. It has the 350 with 700R4 in it, with decent all terrain tires that offer excellent mileage, but which don't howl when I fly down the highway. No lift kit, and a fiberglass cap on the back. I can get just about 21 mpg if I watch myself and am not hauling anything too heavy. On a bad day I get 15.
Here's what I did:
First modification after buying the truck 17 years ago was to tighten up the front end. Remove the slop with new ball joints, tie rods/ends, new gas shocks all around with coil overs in the back. All of this reduces movement of the body and the need to correct steering, all of which requires a little more effort on the part of the engine.
Then I milled myself a spacer for under the TBI, I used aluminum but anything that is gas resistant like plastic will work just fine. In fact, on my old 73 F100 Highboy with a 360 engine benefited with just a smaller one. But anyway, back to the GMC. I added a hotter coil, 8.5 mm plug wires and a new ESC module along with a quality cap and rotor with brass terminals ( I always went with Blue Streak Standard until the quality dropped). Then replace the spark plugs with quality ones, like AC Delco or NGK. With a hotter coil you can open the gap a little bit more.
And after I installed a cooler T-Stat along with a Jet Thermo Power chip, I felt an increase in power, and it also helped mileage. As for the silencer tube, well, the inside can be opened up to act better but look stock. Then I went with a K&N filter for air and oil, and synthetic fluids all over the vehicle.
I have a few more secrets that I just can't get into, but I will say that the truck will pass any emissions test as no equipment is missing.
Good luck