People often ask us for the best expansion combinations for Dominion. In truth, the game designers made sure that all Dominion expansions mix together well. The expansions all combine well both thematically and in terms of game mechanics. The game never breaks if you combine cards from different sets together.
However, some expansions are especially great to combine with others because they put the other expansions in a new light. For us, these are the expansions that really shake up the game: Prosperity, Renaissance and Empires. These are also the top 3 in our ranking of all Dominion expansions.
As we explain in our ranking, these three games shake up Dominion in a fundamental yet elegant way. Prosperity adds Colonies and Platinum, which makes games longer and therefore allows for much more powerful engine strategies. Renaissance adds Coffers and Villagers and Events, and especially its events challenge players to practice new strategies. And Empires adds Landmarks which change the scoring mechanisms so that players have no choice but to adapt their strategies.
Therefore, we think that Prosperity, Renaissance and Empires are a great combination with any of the other expansions. So whichever expansions you already own, you would do good to add one of these three sets to your collection.