My truck ran better when I ran E85 although it was a bit balky when the weather was cold. Mpgs dropped a bit, but it burned cleaner and damn sure was cheaper. It's only subsidized because of the ArcherDanielsMidland and Cargill lobbies that have large stocks of corn, whereas it could be made cheaper from sources like sweet potatoes.
Aside from driving habits, the number one thing for squeezing out the most mpgs is tire pressure -- put it at recommended, then another 5psi or so over that, or just at the very top of the allowed range for your tires. Low Rolling Resistance tires help too, but not as much as the tire pressure, and they are a trade-off with less traction that you might not can justify in the winter.
Synthetic crankcase oil helps a bit, synthetic gear oil would help if you had a manual (I've put that in before). Change your plugs and gap correctly, change your air filter -- that aint hard at all. Put in a bit of Lucas fuel injector cleaner in your tank. The main sensor that will mess you up on a vehicle with a few yrs is the O2 sensor. When that starts to go bad, your engine gets confused about how much fuel is needed to be pushed thru. You may have one or two O2 sensors but get autozone to check if bad then you can change them. Next thing along those lines is EGR valve -- it can get caked with carbon, but you can clean it, just buy a fresh gasket for putting it back on.
There's no one silver bullet for any of this but it all helps. But if you have a bad mpg vehicle, none of this will help you much. A 10-15% increase on 12 mpg aint squat; 10-15% on 40 mpgs just sounds a little better.
