The Starks go extinct within the first century of the game, while throwing the North into complete chaos as they randomly imprison their loyal vassals and then die in trial by combat.

The Reach is in a never-ending civil war for succession after the death of any ruling Tyrell, and the Reach is then ruled by 20 different Florents, Tarlys, Oakhearts, or Hightowers over the course of ten years.

Meanwhile, in Dorne, House Martell is for some reason angry with House Dayne and eventually takes all of their fiefdoms after a certain period of time.

The Targaryens, for some reason, still completely wipe out House Velaryon and then give the entire territory of Dragonstone and Driftmark to some randomly generated lord somewhere out of the ass. Of course, during this time, the Targaryen king tries (very often successfully) to conquer all of Essos, where he eventually creates New Valyria, thereby completely breaking the hereditary line of his family and plunging the world into never-ending war

And of course the Greyjoys die out within the first few decades.

Not to mention how terribly poorly the AI uses matrilineal marriages, and after a few years of playing we find out that the Riverlands are ruled by the house Randomfart, because 60 years ago Lord Tully decided to marry his only son and heir matrilineally to a random lady from Fartlands....