i don't know if you've commenced on this project or not; If you have, great. Maybe you can give us some updates.
If not:
Wanting 300HP, 25mpg, 87octane AND in a full size pickup is a very tall order. Not impossible, but difficult. If you have said 300hp, 20mpg, then it would be pretty easy.
A good exhaust system is a must. Headers will probably be a must. Where do you live? Do you have emmissions testing?
You didn't say anything gear ratios, so go with a 2.41 if possible. If too impractical, then go with the largest diameter tires that will fit(and some pretty large ones will fit).
Believe or not, i would start with the truck itself:
We all (hopefully) know that driving with the tailgate down doesn't help, in fact hinders, gas mileage. Slowing down helps too, but with your desire for 300hp i don't think that's an option for you. No offense intended.
Is the truck lowered? As much as i dislike lowered trucks, i admit that they do get better mileage all other things being equal. A lowered vehicle achieves better aerodynamic Cd.
This project is not impossible. Give me a few days to think about.
In the meantime, be thinking about Independant runner systems and weber carbs. This may be your solution.
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