Why is Spain #1
With most civilizations you're directed in a certain direction by the unique ability, unit, improvement and/or building and I'm not nearly enough of a cool and original rebel to go against the obvious designer intentions. With Spain, you could get a variety of possible bonuses or none at all from whatever natural wonders you find and this gives every game a different character. It's refreshing not knowing. Your start could be absolutely dominant or complete garbage and it's out of your hands. And when it is a good start, forget about it. Throw in the Conquistador's ability to both fight and settle and the Tercio, which is, well, something and they're my clear favorite. I've played them enough to have actually gotten a workable Krakatoa, for goodness sake.
As for Isabella, I think the following amazing image is all you need to know.
Honestly, it's not even close.
Most Memorable Game as Spain?
Finding King Solomon's mines in the first ten turns, settling a city with the 500 gold and building almost every early wonder, even ones I wouldn't normally even consider like Temple of Artemis and the Great Wall. The city's production was absolutely insane even with a few citizens. The neighboring Mayans, perhaps rightly sensing that I wasn't going to share when it came to bronze age monoliths declared war, melted against some hastily raised defenses and ended up getting conquered. Later I founded a city on a City State island and got Krakatoa (!), adding a ridiculous science city to go with the production one en route to winning a cultural victory.