Mayo is very easy to navigate and everyone is helpful if you have questions or need help to find your way around. Once you get acclimated to the setup, it is easy.
Lots of eating options at Mayo. The cafeteria is fine, plus there are also lots of other options if you venture further in the Subway. Lots of chains (Dairy Queen, Quizno’s, Subway and coffee places like Starbucks, Dunkin Donuts, Caribou) plus some very good local places.
If your appointments are in the Mayo or Gonda buildings (or the other nearby buildings), I would recommend staying in the hotels nearby. If you have lots of appointments, you can easily go back to the hotel to rest, etc. While I have stayed at hotels further out plenty of times and have used their free shuttles with no issue, what so ever, for first visits, I would recommend staying in the hotels downtown that are connected by the Subway.
Good luck! Mayo is amazing and unlike any other medical facility.