Torque.

Torque production is a direct reflection of volumetric efficiency. Volumetric effciency is making the most power for a given fuel consumption.

Then engine combo that makes the most torque over the broadest range will produce the most mileage while being the most fun to drive in the lowest rpm range which will allow it to live the longest life.

Certainly smaller displacments use less fuel than larger discplaments, but I would not build a 273 over a 360 for that single point. Also, there is a sweet spot for piston speeds that can be demonstrated in a pumping efficiencies map. Compression is a big factor as well since the more you squeeze the charge, the more power you get from it, the less displacement you need because you're using the fuel more completely. Combine that with swirl and squish and you can get a lot of thermal efficiencies out of a gas engine.

Back to your personal combo...

I'd go 5.2 or 5.9 if they are readily available. If I had to choose, I'd go 360 first with some high swirl heads and as much compression as you're wlling to live with because it is a large torque engine. 650 AFB carb. These are easy to tune and you can really dial in the cruise and power circuits without a lot of trouble. Parts are readily available across the country. Ignition, maybe a stock dizzy with a a chrome box to reduce failure liability, and a decent coil. Simple, effective. small tube headers with dual exhaust and a manual trans of your choice.

Personal note on ignition-in my drag car I ran a stock system with a Jacobs coil, a Crane system with a stock dizzy, and a comlete MSD Digital 6 system. Between all three there was no appreciable difference in idle quality, e.t., or mph. That tells me there is not a huge gap in ignition capability among the popular options.

Using the above approach, I've been able to get the 440 in my truck regularly run in mid to high teens for mileage with a carb, 3 spd auto, and 4:11 gears while pulling like a diesel and being an overall low maintanence build.