Pilots play this game all the time. We also have move levers, buttons and gages to see what is happening.
It all depends on the vehicle, the engine and what you are trying to do.
First, lets take out the stuff that adds needless complication for the question, supper chargers, blowers, turbo chargers, direct fuel injection ( like a diesel, straight into the combustion chamber ) and we will stay with carburetors and what most call fuel injection which sprays the fuel in just upstream form the intake valve.
We can see oil temp, head temp, exhaust gas temp, exact ground speed ( GPS ) we have very actuate fuel flow meters, manifold pressure gages and tachometers. We also have a constant speed transmissions ( constant speed propellers ) and we can control the mixture.
Now we can set it up where we take out as many of the variables as possible and see what is left.
We are looking for best fuel economy. ( slowest burn rate ) which will give us the longest time aloft.
We also are looking for the best miles per gallon.
we also have the restriction that we must remain in the air so that puts reasonable restrictions on practicality.
Now we go to an altitude where with a wide open throttle, we only can have say 24 inches of manifold pressure. ( throttle is out of the equation ) we set the RPM to say 2400. Now this is a good place for engine life and reliability for the most part on small aircraft piston engines. So, since we are straight and level and there is no wind and we are trimmed perfectly, we have taken the load ( wind resistance and grade ) out of the equation.
So now we have set the engine for the best known conditions of temp mixture and are getting a known burn with a known speed.
Now we will change just one thing, the load. We will use the propeller to slow the engine to 2200 RPM, ( increase the load ) and again reset the mixture to the best possible place. The fuel burn rate will be less. But we will be going slower, We can do this until we can just barely fly and we will get less and less fuel burned so our time aloft will be maximized.
*If we go the other way and increase RPM and reset to ideal conditions, we will be burning more fuel. There is also a point in this direction that the increase flue burn rate will not give enough increase in speed to improve the MPG.
This sweet spot is usually a very narrow range and within the confines of practical driving, you will gain more by constant throttle position than in increase in RPM.*
If we continue to reduce RPM, there is a price. There will be a point that we will be slowed down enough that we will actually cover less miles. There is a difference between best range and best duration. For each plane / engine combination, it is different but it is easy to see. There is always a trade off on what can realistically be done, you should not drive at about 40 MPH say on the interstate. You would need two lunches at least. For miles \ gallon, fixed throttle position is best within the restrictions of engine health, safety concerns, MPG etc. ( 25 in a 75 is not safe )
The computer controls in the newer cars do a great job with the bad situations that cars normally operate under.
For the real world, close attention to fuel burn over the same road day in and day out will show you what you can actually do that will get you the best MPG.
If all things are at their best efficiency, the only way to go faster or pull a heavier load is to use more energy. ( fuel )
Remember, a lot of theory is absolutely useless in practical application.
We also have totally left out the concern of the value of your time or the need to move in a fixed time.
*:: The only time you have too much fuel is when you are on fire. ::
:: If you want to go faster, you spend more money. :: *