The three men who would normally be in the conversation of best luchadors would be Santo, Blue Demon and Mil Mascaras. Of those three, only Mascaras ever really seriously wrestled in the United States, but beat both the WWWF and NWA World Champions when he did so. I'd say a Mexican wrestler beating the WWWF Champion in MSG is a pretty big deal. That's a pretty big achievement there, and his notoriety at home and in Japan would probably make him as popular within the wrestling world as a whole as Mysterio is now. I However, the exposure then is obviously different to now, and it leads the argument to a different level. So it greatly depends on what you are trying to say. Have more people seen Rey Mysterio wrestle than any other luchador globally? Yes, probably. But more people have seen Duane Gill wrestle than ever watched Lou Thesz, that doesn't make him better, you have to contextualise what they were doing.
Which brings us to Santo and Blue Demon. Well actually just Santo, because an oversimplified analogy could be made between their relationship and that of Austin and The Rock. There is absolutely no argument that Santo is the biggest name in Mexican wrestling, having crossed into the mainstream fully. The attendance at his funeral was more than 10,000, and there's no other wrestler anywhere that can claim that dedication.
Santo never seriously went to America, it's true, but why would he? Mexican wrestling was more popular than American wrestling at the time, and few wrestlers made much money there, and fewer still went into any mainstream things. Santo was the most popular wrestler in the world in the early 1950s, in terms of being able to draw people to arenas on a nightly basis. That being said, Rey Mysterio is beamed into more homes on a weekly basis than Santo was.
Ultimately, it depends on what you are trying to say. I mean, sure more people in the world know who Rey Mysterio is than who El Santo. More people watch him. But that has a hell of a lot to do with technological advances. Ridiculous examples aside, what about John Cena? There are villages in Romania, in the arse end of nowhere, where the only English words the kids know are "John" and "Cena". Does that make him better than Hulk Hogan, just because WWE is more accessible internationally than it was in 1985? I don't think so.
I really don't know if I agree with you or not. I understand the arguments, but it just doesn't sit well to think that the answer to this question is anyone but Santo. Mysterio is more popular globally, and thanks to the WWE's ubiquity has wrestled in more markets, but Santo was adored by a much bigger percentage of the people he could ever hope to perform in front of, crossed over to the mainstream, and has statues erected in his honour. I think if Mysterio had been the biggest star in the WWE at any point in his career, then I'd go with him. As he hasn't, I think it's Santo.