Into the weeds engine design for fuel efficiency discussion.

Phreakish said
Fuel is energy. Engines turn it into work/power. Work or power required is determined by drag (both aero and friction) and incline.
Proper gear choice and driveline loss will make any two engines near identical, assuming both will produce power in excess of what's strictly required. A smaller engine has far fewer challenges to efficient combustion and extraction of that energy. From friction down to the dynamics in the combustion chamber. Larger bores, longer strokes, and engine weight will all play into the calculation and so yes there is a balance, but the 'smallest capable design' will always win the fuel consumption competition.

An over-sized engine will generally be more durable and easier to operate. But that has exactly zero to do with maximizing MPGs.

Exactly. Now if we look at engine displacement and watch the carburetor. Holley has a power valve that most seem.to relate to easily. The Edelbrock and Rochester accomplish the same thing in a different way, power fuel enrichment. If we choose an engine of sufficient displacement to accomplish our requirements, without getting into the enrichment strategies, we will likely get better fuel economy. The new Chev 1500 trucks with the 2.7L turbo banger engine are an inyeresting case study. Essentially if you jam 5.4L of air through a 2.7L engine, you should get the equivalent power or torque out. Watching towing videos of those, they seem to work out really well for towing and economy. When not towing the economy should be much better than a 5.4L, or in the General's case, 5.3L V8. That cylinder deactivation, DoD or AFM appears to be problematic with engine noise and failed lifters.
It will be interesting to see how the Stellantis Hurricane engine works out. I wonder how re engineering a slant six with 7 main bearings and a DOHC 4 valve hesd would work out. Seems to be close to what the Hurricane is but stood up. An A body or say Volare with a 225 and DOHC would still be able to have a low hood line, with the advantages of the DOHC breathing. A head could be made by cutting up Mazda or Ford 2.3 or 2.5 heads and weld them together. Custom cams would be expensive for a one off, but it would be an interesting experiment. A timing cover would need to be fabricated. Could even try the VVT. The Mazda/Ford bores fit in to the realm of O/S for a slant. Compression height would be a sticking point. Maybe the 2.2L turbo pistons.