snip
Reducing European nations exploring, conquering and colonizing much of the world to "it was a fluke since they brought smallpox" is one way of looking at it, but it's not one I agree with. It certainly played a big part, as did the timing of the Spaniards arrival in some places, like the Inca Empire. But that doesn't mean that a larger commitment from Spain would eventually have led to the same result. I'm not saying that the book Guns, Germs and Steel has all the answers, but I find the explanations in it a lot more creditable than your conclusion that "Nothing in this period (1399-1821) pre-determined European domination of the world. Nothing."
And just to be clear, I'm not a big fan of how easy it often is in the game for a European country to conquer outside of Europe. This is an area I personally like to see some improvements in and hopefully we will be able to deliver that. But it's always a delicate balance since most players don't want to see African invasions of Europe.