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I have done a little bit of reading on a similar subject, but it was concerned with power and not with efficiency. If you check F1 engines from about a decade ago, you'll find that everyone settled on 10-cylinder engines. I forget which displacement formula this was, but it was not in any of the forced-induction eras. (Possibly 3-liter?)
It turned out that there was a definite maximum in the power produced by a V10 over the V8 and V12 designs, which is why everyone eventually went to the V10. I believe it was a tradeoff in internal friction with higher numbers of cylinders versus better breathing with higher numbers of cylinders. There could have been something with the lower overall masses of the moving parts when you have a larger number of cylinders.
So the differences: This was cost-no-object engineering, optimizing only for power and not at all for efficiency.
I suspect that there are similar considerations and tradeoffs when talking about efficiency, but I don't really know exactly what they would be.
I'm pretty sure a large I4 would be more efficient than a little V8 though.
-soD
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