Back in the days I had a '66 Econoline van. Basic 200 cu. in six, manual everything, and of course the aerodynamics of a rather large brick.
Drove it from Mississippi to California circa 1969 and returned about a year later.
Stuffed with everything I owned (actually not a heckuva lot, but many tools and other heavy items), it knocked out highway mileage of 20+. Never really checked it around town, as we're talking gas prices at that time of about 3 gallons for a buck and small change. (Yeah, don't we all just wish!)
Looking back over a long and checkered history of vehicles I've owned, it seems the majority of them have been inline sixes, and a couple straight 8s. Not a conscious decision on my part, just seemed to work out that way.
If it were me, I'd think about building up the six. The majority of them (excepting the 144ci, I think?) have a bulletproof bottom end with a rousing SEVEN main bearings!
Horsepower-wise, the stumbling block would be the cylinder head design. Still, the stock head/integral manifold can be worked with to some extent. If major horsepower is your goal, there are crossflow heads available (off an Australian version of the engine if I remember correctly) on up to an aftermarket 12-port aluminum head. Quite a few goodies available for the engines.
If nothing else, you'd have something different! Guess I never liked to run with the herd.
Good luck with your project!
Retro in Mississippi