The AtomicAss,
It is already clear that a small cylinder is more thermally efficient than a larger one. Given both are running similar octane gas and similarily aspirated, a smaller piston crown and combustion chamber will probably be more thermally efficient for many reasons. But it's not so simple. More cylinders means more friction and weight, all big negatives to efficiency. Further, the added complexity and packaging problems of too many cylinders is prohibitive. I can imagine an 8 cylinder 1340 cc Busa but it would be quite heavy. Realize also that small pistons need high revs to get good power, which reduces thermal efficiency and fuel economy.
I can imagine a V6 motorcycle, in fact there are (or have been) engines like this already, or maybe even a V8. I think thermal efficiency would best come from using some of the heat energy typically wasted, like a turbo charger. I suppose it would be possible to have a V4 gas engine with 2 additional steam powered cylinders with the steam generated from the waste heat from the V4. But again there is the complexity and need to either carry a water supply or condenser system to recirculate the water for the steam engine. So I'm not sure there are many options here that offer big gains in efficiency.
Obviously a 2 stroke is the biggest pig when it comes to any kind of efficiency. A direct injected 2 stroke could work, as a smaller displacement 2 stroke can produce big power and direct injection would limit some of the inherent inefficiencies of a 2 stroker. 4 stroke is a good compromise. Increasing the strokes means more unpowered strokes. This can be overcome with more cylinders and offset cranks like the Yamaha R1. Adding cylinders and adding power pulses may help thermal efficiency but it will not be good for power. Also an engine like this would need higher rpms.
Truth be told 150 mpg is well within current technology in a 1340cc motorcycle engine. Better injection technology, dead cylinders (drop 2 off in low demand), and gearing could all make 150 mpg possible. The real ticket to thermal efficiency is running the engine at a constant rpm. This could be done with a CVT. The trick to gas mileage is going hybrid.
As for money, this would cost millions, not $10,000. If you want to see what developing and engine costs, watch the documentary on the MotoGP engine effort MotoCZ made.