Right, assuming chain displacement is not factored, anyone would be hard pushed to tell the difference between gear overlaps in resistance. Impossible. The main resistance on a bike is the blob of a human on top.
Mechanically, it's better to keep a straighter chain, and in theory, bigger sprockets and chain rings spread load, but you would not notice it on a bike unless the chain was at a skewed angle. Running big to big and small small isn't good on the chain, and can be rough.
Running gears and chains at high angles of deflection promotes wear.
I can't tell the difference in resistance from switching a 39x16 to a 53x19, slight gear ratio change but no difference, even on an old bike, but rather well maintained one. That's my overlap gear.