Each engine has a torque/fuel curve. There will be a "sweet spot" where the engine delivers the most torque per unit fuel.
Maximum fuel economy will be realized by gearing the vehicle such that the power produced at this RPM will exactly equal the power required to move the vehicle at the given speed in the highest gear.
Remember that the power required is the sum of all the power losses to include: heat losses in the power train past the engine, rolling resistance (tires) and aerodynamic losses.
If one will simply look at the heat loss figures (often difficult to locate) for transmissions furnished by their manufacturers, one can EASILY determine the largest gain in fuel economy is virtually always obtained by junking the automatic transmission in favor of a standard!
And my the way, my iron head V-8 with 10.3 compression and dual 4 barrel carbs went from occasionally pinging on 93 octane to running with no pinging under normal load with 87 octane and pulling a 16 foot trailer with 2 L & G tractors with no pinging at 91 octane JUST by junking the automatic. No other changes. Fuel economy also increased by approximately 30 percent at normal highway speeds without the trailer.
Yes, the total gearing is very important, but less so than being lazy with an automatic to shift for you.
My opinion, yes, but it has proved to be true with every transmission swap we have done in the last 40 plus years.
Jon.