Fluxx by Looney Labs is, I think, an increasingly well known card game with a growing number of expansions and spinoffs. While I've played Zombie Fluxx, Cthulhu Fluxx, Star Fluxx, and Monty Python Fluxx, I have a strong soft spot for the original game and first spinoff EcoFluxx.
In Fluxx, the rules are ever changing, including the conditions for victory. There are five main types of cards: Rules, Actions, Keepers, Goals, and Creepers. The game starts with players having a hand of 3 cards and a basic rule in play: draw one, play one. When yellow Rules cards enter a player's hand, they can play them to change the rules, which can result in things such as larger hand size, more cards drawn or played, or limits on Keepers on the table. Keepers, the green cards, are generally the key to winning and are objects or concepts such as Earth, War, Cake, Trees, or Party. Goals, colored pink, typically ask for two Keepers within a theme, such as Earth and Peace for the Goal "World Peace." Blue Action cards let you do something, such as "swap hands with another player" or "draw two play one." Creepers are colored black and generally block a player's chance at victory; to be perfectly honest, I generally play without them because my group started playing Fluxx far enough back that they didn't exist for most of our experience with the game, but they definitely add another layer of complexity.
The game is relatively simple in that context, but because players are constantly changing the goals and rules, it can be hard to keep up. Which, I think, is a big part of the value of Fluxx in all its varieties. It teaches players to be flexible, and to think strategically about when they play their cards, because what might be a great hand one turn might be lackluster the next. Games of Fluxx sometimes take as little as two minutes or as long as two hours. Fluxx adapts well to both small and large numbers of players, especially when combining two or more sets, as I regularly do with Fluxx and EcoFluxx. Even better, Fluxx is easy to transport, quick to set up, and simple to learn, making it great for trips and new groups. All these things add up to create one of the mainstays of my game collection that I can play with pretty much anyone.