The larger bore sizes have lower cylinder wall surface area as a percentage of displacement, so they will also have higher efficiency. Optimal piston speed is, as Frank already posted, the ideal point between the excess losses of the two extremes.
Other factors are the harmonics of induction and exhaust pulses and how they can reduce pressure waves which would affect in cylinder compression and exhaust scavenging. Also the amount of residual exhaust remaining in the combustion chamber which would tend to increase efficiency to a point, one reason why highly scavenged exhausts usually produce lower mileage.
Combining gas and diesel engines could yield best of both worlds
regards
Mech