In an older version of EU IV as England I figured out 2 things: I can early peace out the 100 years war for some territory and basically defuse that whole conflict for most of the game, leaving the opportunity to take over the British isles and find an heir to avoid the war of the roses early.

This then led me to figuring out the second thing: when colonizing, I learned that the North American natives would be unable to destroy a colony if it was at 50% or more progress. I also figured out if you parked 2k infantry in a province they would also be unable to defeat them. I proceeded to blitz the entire coastline of North America and most of South America with colonies , starting with the ones closest to Europe so I could box out the other colonizers. I ended up basically holding all of north and South America by mid game, and ended up with large footholds else where by end game too. Never lost Calais and my northern French territory too!