Is there a fundamental limitation that prevents large countries from ever being as effective as, say, Estonia or Singapore?
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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.
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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You need size to have more specialization, but I don't know if you need larger countries. Larger cities is more likely. Intel probably could have had scale in a smaller country as well
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To restate my tweet: to raise ~10^9 dollars for a fab was easier in the US in the 80s than any other country, purely because of the scale of the capital markets. Much less true now: it's a lot easier for capital to flow across borders. (This is speculative, but I believe true)
End of conversation
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