Certainly not scientific, but my original 427 build for my car was .040 over center oiler, Isky EE-390 (250@.050, 108 LSA on 105) 1000 Holley, Portosonic, Hookers, iron heads and a close ratio 4 speed
With a 3.70 gear and 28 inch tall tires, from Las Vegas, NV to Bishop, CA , 540 miles round trip, cruising speed limit or higher on the way up and hauling ass on the way back, I got 14.1 MPG
With a 3.00 gear, same setup completely, Las Vegas, to Anaheim, CA, also 540 miles round trip, cruising speed limit or higher, but not horsing around, I got 13.0 MPG
Now the roads were way different, the first run went up and down a bunch of good hills and much less traffic, but there certainly is a sweet spot.
Funny though, now that I have EFI, more cubes, a much better setup I'd expect on the highway....I have no place to go
From Omaha NE to
? everywhere I think of tends to have a potential for hail or some other ugly weather....go figure