Last July my wife and I traded our permanent home for the experience of living semi-permanently in a new US city each month while launching an online business. Almost by accident, we became digital nomads (sans exotic, inexpensive southeast Asian destinations).
Routines are constantly disrupted. When you arrive in a new city, you are forced to give up certain activities and remain open to a new way of doing things.
Nurturing friendships takes real effort, thought, and energy when nearly all of your friends are long-distance.