My Challenge to U /6ers....

I'd say find a manual transmission, fuel inject it at the least, and keep the engine maintained and clean. FI gives the best gas adjustment, direct FI and turbo makes it better. The manual prevents the power loss due to switching energies.
Check the diff, and match everything to the fuel injection so it stays smooth. Don't port the heads, you will want the ledges for mileage. And I'd only use one type of fuel- most computers and carbs don't adjust for the different levels of fuel (I didn't say that right).
That would give you a great basis for all the other options, which push the 1500 limit.
I have a ram 2500 diesel work truck and I get 23-26 mpg. You drive a v-style engine, you ride behind a straight. It's all about the flow of power.