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.