My thoughts are to use water injection along with raising the compression ratio to a much higher value. This would normally cause detonation, but the water injection would prevent it. And also as you said, using a custom EFI system, you could run a very lean mixture at cruise speed and use the water injection to prevent overheating of the cylinders.
I think the downside (besides the added complexity for probably a small gain), is having to add the weight of the water and/or refill it often.
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