Correct me if I'm wrong but an engine is most efficient making about 75-80% of its power as the throttle is more open filling the cylinders more and raising the effective compression ratio. This would mean 4 cylinders would be more efficient at cruise than 8 because the cylinders under power are operating at a higher effective CR. It would follow that your engine would be even more efficient on 2 cyls. at cruise as you would be close to that 75-80% but the engine would probably be objectionable from a smoothness standpoint.

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1954 Chevrolet Belair
1969 Ford Mustang
The Silver Buick