-The European AI don't really found colonies. In my game, the French placed two colonies in Canada early on, but those were the only colonies I didn't found in 1585. The Native American civs & the French were the only ones to place new cities.
I am not having that problem in the version of the game that I am playing. The Portuguese have several colonies in North America, a one in the Caribbean, while the French, English, and Spanish all have a presence there. It might be a quirk in the starting RNG for the game.
-Pollution is a problem. It was popping up all over England & Ireland. Perhaps it's intended to limit population, but it would be better to adjust food production rather than the player have to send Workers to fight pollution every turn. I didn't want to, or need to, build Mills because of the pollution already rampant & because I didn't really need more production.
You can evade the pollution problem by changing the settings for Town and City in the General Settings menu. I have Town set for 9 and City for 21, with no ability except for Shakespeare's Theater to build a city larger than size 2. I use the hospitals solely as a basis for getting Battlefield Medicine.
-It seems very odd to have the Berbers in the New World with two cities in 1490... Looks like you did this to simulate the pirate havens. I think that if the Europeans can be made to actually colonize the Americas, piracy will follow. They are building pirate ships in Europe.
I simply took those out, with no problems for game play. I have privateers running all over the Atlantic, and I have yet to get a ship through the Straits of Gibraltar into the Med. I may change the setting of the Ship-of-the-Line to allow for some carrying of cargo so as to get treasure back to Europe as the Dutch. Running the gauntlet past England and France is a bit tough.
-The Medicine tech doesn't seem to do anything.
Make it the Tech Prerequisite for building the Battlefield Medicine Wonder if you wish it to do something, along with having the Wonder give a happiness boost to the building city and a smaller happiness boost to the rest of your cities.
-Most of the Great Wonders require a resource that England does not have access to. It's odd that England can't build Shakespeare's Theater or the Adam Smith wonder, especially since they were historically English.
I will have to look at the latest download to see why that is. I am not having that problem in the modified version of the first download that I have been playing. If you want to restrict who can build a Wonder, you can adjust the government type, or add a country-specific resource needed to build it. To limit the English Wonders to just the English, set the government type for building to Protestant Monarchy, and you would only be competing with the Dutch if you add the Colonial Nations resource as a building requirement. I did get tired of the Berbers building Luther's 95 Thesis so I took steps to limit who could build what.
-IIRC, the Great Wonders are all or mostly English ones. Perhaps you can find some appropriate wonders for the other civs.
There are 8 Great Wonders, only 3 of which are English: Shakespeare's Theater, Newton's University, and Smith's Trading Company. Three are Italian, the Sistine Chapel, Copernicus' Observatory, and Leonardo's Workshop, one is Spanish, Magellan's Voyage, and one is German, Luther's 95 Thesis. The Portuguese start the game with Dias' Voyage as a 9th Wonder.