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berlinonaut: You're right, there are too many variables, and the combined effect of all variables can't be placed at the wheel size's door.
Because speed record velomobiles routinely use small wheels, we can reasonably dismiss the dominance of wheel size on the overall equation. I would call wind resistance first because it becomes completely dominant at peloton speeds, and frame stiffness second. I had a Birdy and though it is a superb folding bike, it is FAR from stiff. You can take the handlebars and twist the whole frame while seated by pushing sideways. It is astounding how much it will flex. Not to mention the suspension.