Hi Doctormario777, welcome to Ecomodder!
I'll try to answer a couple, if I can.
1. What kind of fuel efficient trucks should I look into?
If you're focusing on efficiency, and not 'truck' so much, then you're looking for a four cylinder manual transmission two wheel drive truck. Brand preference is really up to you, many people start with S10/Isuzu, Ranger/Mazda, or pre-Tacoma Toyota trucks. Something in the 2.0L-3.4L range.
2. Is a v4 or a v6 more efficient at highway speed?
Depends on the driver more than the cylinders. You can squeeze decent mileage out of a V6, but for your 400-miles a week trek you're much better off with a four cylinder. A V6 will get you to highway speed quicker, but a four banger will do it cheaper. And that's the goal, right?
3. What is the best fuel economy I could expect from a light to moderately modded 1978 f100?
Uhm, not very good. There is a member on here modifying an older Ford like that, but in my mind, raising a 12MPG truck to 16MPG isn't as cost-effective as starting with a 27MPG truck. It sounds like you'd rather leave the F100 parked, drive the Challenger for fun, and a fuel sipper to go see the wife, correct?
Read the "100+ Hypermiling Tips" on the top of this page. Altering your driving habits will gain you more MPG than any modification you can do, and it's free!