Highly subjective question.
There is no definitive answer, and it depends what part of the world we are looking at. The Americas, Japan and modern-day Russia were all split into little city-states constantly annexing and warring against each other. The biggest technological leaps were mostly (but not entirely) in Western Europe and the Middle East. Africa and eastern europe were very rural and 'undeveloped'.
The middle east had the Byzantine Empire during the first part of the 15th Century, but that had been destroyed soon after despite covering a huge amount of land. The Ottoman Empire (the Turks) were increasing in power but also near their end - around the turn of the century they began to collapse.
This leaves China and western europe. I mean, technology and civilisation was advancing in other places (e.g. Korea), but China had a larger land mass... but then again had very little territorial expansion, despite developing agriculture and gunpowder.
One couldn't say western europe was a 'major player', because western europe was split into France, England, Spain, Austria, all the German and Italian States including the Papacy...
Spain """discovered""" the americas, the germans invented and developed printing
The Habsburg Dynasty had a huge amount of power, but this was a dynasty covering several countries - not the kind of nation-state we know today. Many 'countries' had varying and often vague degrees of independence from their neighbours or rulers. What you have to understand is that, for the average peasant, the major player was their employer. For the tennant, the landlord. For the man-at-arms, their lord or baron etc. For the landowner, the monarch. For the average king, the only person, power or country they were answerable to was the Pope.
Understand that western europe was "united" (yeah right) as Christendom in the catholic church, which was 'ruled' (sort of) by the pope. In the end, the pope could have theoretically got away with ordering a crusade against any european or indeed any country in the world. Religion was integral in every-day life from serf to emperor.
The 'country' the pope almost always came from was Italy (although the french kept electing their own, each claiming they were the 'real' pope), so you could theorise "Italy" was the major player. However, Italy had what I call the "Am I A State?" problem where many parts were separate countries, many parts liked to think they were and many wanted to be. Also, Italy was very rural and had terrible agriculture for the most part, developement and technology were scarce.
The "Papal States" at the heart of Italy (including Rome and a bunch of others like Umbria, Bologna, Ferrara) were sort of united by having the pope as their "head monarch" (though each state was often ruled by a separate royal family). These are not states like the modern USA, these are states like the United Nations... except with a pope.
Overall if I had to come up with one country, I'd say the Papal States, but as you (hopefully) read above, they weren't really a country. Which states were "major playerS" is easier - France, Spain, The Holy Roman Empire (all the germans under the habsburg family), The Papacy (more of an institution than a country), outside of there one could say China for the far east and the Mayan peoples for the americas.
Sources: amateur historian, particularly in medieval military, also doing an A-level in 16th century politics (for which I learnt a bit about the 15th century).
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