Pistongone - very good point about 6 seats. But with 6 seats loaded with "present day sized" people you have just enough range to get to Le Touquet and back
May be good for Vietnamese refugees though
Realistically, a 6-seater will very rarely be full, unless one is running some dodgy operation.
Fundamentally, an engine operated at peak EGT, or lean of peak, is going to deliver X HP per gallon/hour. Something like 10-15HP per GPH I think. It doesn't matter what size it is; the bigger the better and one with fewer cylinders and bigger cylinders will be better. That's why an IO-540 in a TB20 delivers at least as many MPG than an IO-320 (?) in a TB9/10. Similar airframe, TB20 has no legs hanging out
There is no free lunch with planes. Everything is a tradeoff against something else.