The city of Sanctuary in Borderlands 2 is very likely a reference to the realm of Sanctuary from the Diablo series. Since Borderlands is a contemporary of Diablo (in a manner), it is rather fitting that such an important place in the game is connected to the realm in which most of the Diablo series takes place. In fact, in Diablo, it is also the place where get almost every (if not every) quest.
In Diablo, Sanctuary was originally created to be a safe realm of peace. It sits in between the Great Heavens and the Burning Hells which are eternally at war. Part way through Borderlands 2, the city of Sanctuary lifts off and starts flying in the sky. It does this to try and escape destruction. From that point on, it sits in between Pandora and the Hyperion base in the sky which are at war with each other.
Interestingly, in both franchises, the character Lilith plays an important role. In Diablo, Lilith is one of the people responsible for the creation of the realm of Sanctuary. In Boarderlands 2, Lilith is partially responsible for the founding of the city and largely responsible for it's flight.