The all-important Principal of Least Astonishment:
Do Whatever Astonishes the User Least.
Elsewise, I would recommend:
Make it easy to use the entire app without touching a mouse.
Provide clear labels that explain what is going on.
Screens are big these days; You don't have to cram everything together. Provide some space. Don't use a drop-down menu when you can use radio buttons. Make fonts big. Make widgets and icons big.
Don't do anything that resembles the Start menu.