Is there a fundamental limitation that prevents large countries from ever being as effective as, say, Estonia or Singapore?
You cherry-picked. Many countries that size aren't effective. So maybe that's your answer: in a world of 7 billion people you can have dozens of Estonia-sized countries, and the best may be pretty good. But you can't have dozens of China-sized countries. More at-bats.
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Incidentally, the reverse may be true. My fave contrarian theory for why Silicon Valley happened in the US is economies of scale: a company like Intel required enormous amounts of capital available (to pay for fabs), so pre-globalization it had to happen in the largest economy
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