Before Conquests, I didn't notice any one Civ being a huge thorn. By the way, turn off culturally linked starting positions to get a wider variety of opponents (and to defeat the American civ "bug"). But now I have an enemy that is truly the worse. The Inca!! If they start on your continent, you have to kill them early or they will ruin you. And if they start on a different continent, they will kill everyone there and become so strong that they will almost definately win by space race. I hate them.