Well, aerodynamic losses increase proportionally to velocity squared. So slower is better.

Friction losses within the drivetrain (ignoring gearing for a moment) are proportional to velocity - but since distance travelled in a given time is also proportional to velocity, that's a wash. Your losses are proportional to distance travelled.

So that leaves the engine and gearbox. The latter is unlikely to have noticeable efficiency differences between gears. The engine is a beast unto itself. Each engine has a different optimal rpm. In general, the lower the rpm that the engine can cruise at without bogging, the better.

But velocity is really not even half the equation.

Acceleration is the major factor. Cruising at 90mph (theoretically of course ) is going to be more efficient than continually fluctuating between 40 and 60 mph because of crappy traffic,

Last year on the way to Cinci my car got its (then) best ever gas mileage when 'cruising' with Rob. Traffic was light and for most of the tank stayed out of the left lane. We didn't exactly drive slow. It hit the 31mpg quoted

Of course, that record was soon forgotten on the way back when my poor car spluttered its way home. (Still beat the city mileage though)

That record stood until recently when I set cruise control at 55mph for about 300miles which managed 35mpg.
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