I second Munchkin, with an addendum that to enjoy most of the humour in its jokes you pretty much have to have an experience with RPGs, preferrably p&p.
I have found
Battlestar Galactica to be a very well made game - easy to get into with simple rules focusing on human interactions. Think poker with aliens. The game really shines with 5+ players, if you can get that many people to play.
For two players,
Twilight Struggle is a fun card-based game about the Cold War. Proxy wars in korea, instilling revolutions in Latin America, fighting over influence in Europe, it's all nicely modelled and fun.
For the more hardcore boardgamers, and/or history nuts,
"Here I Stand" might be of interest. Six powers, each trying to gain dominance in XVI century Europe during the Reformation period. Mixes a relatively simplified combat, card-driven mechanics and point-to-point map with interesting rules trying to model religious stuggle of the time. Each side(Ottomans, Papacy, Protestant, English, France & Hapsburgs) plays quite differently, with its own goals and "special skillz"(will Henry VIII produce a male heir? will Barbarossa terrorise the Mediterranean with his fleet of Barbary corsairs? How many protestants can the Pope burn at the stake?). Not for a casual gamer, though, as the rules are numerous and take serious studying to wrap one's head around them.
Fans of Napoleonic period might want to check out the eponymously named
"Napoleonic Wars" or
"Empires in Arms". The first one being very similiar in many aspects of its mechanics to HIS, lending it a certain degree of simplicity, the second one much more detailed and wargame'y - expect a behemoth of a rulebook, lots of counters, detailed map, in-depth combat mechanics and easily over 24h per game.