Mostly on a recommendation by Wil Wheaton I got Dominion [buy at amazon.com] for Christmas this year. Luckily Ned was around and was into playing or I might not have opened it up right away! Dominion is a pretty good card game. I'm calling it a card game because the big box it comes in houses only the 5 decks of cards which are this game's only components if you don't count the rules sheet.
The box also serves as convenient storage so you can keep the various card types in separate sections and not end up having to hunt through 250 cards for them every time you play.
Unlike collectible card games (CCGs), players begin a game of Dominion with the exact same deck and 'buy' cards from the 'supply' (a subset of the various card types you elect to play with) as your turns proceed. This is great, as players acquire more cards their decks evolve and become more different with each turn. Luckily, you don't have to know anything about CCGs to play Dominion, but the game is simple and the cards don't offer the same kind of in-depth allure of a typical CCG.
To win in Dominion a player must have the most 'victory points' (represented by land cards) when certain stacks of cards in the supply are exhausted. Having a lot of victory points is a double edged sword because unlike money cards or actions cards, they serve no other purpose than to take up valuable space in your 5 card hand each turn. In other words, having a lot of victory points is great since you need them to win, but is also bad because theres a greater chance that your hand will have those and not the cards you need to attack or buy more cards each turn.
Card counters can really benefit in this game - knowing exactly how many victory points your opponent has acquired over time might allow you to pace your own purchases, or remembering the number of Militia for instance.
There is a serious lack of player interaction in the game, it isn't Settlers of Catan for instance - there is no 'trade' round, or any combat. Each player takes a turn playing an action (or as the game proceeds chaining multiple actions), buying more cards, and racing against time to build the best deck. It's quick (a game might take as long as an hour until you get used to playing), and fun, and you can learn how to play in far less time than your average CCG.
Read more in-depth about Dominion at Boardgamegeek