There are small differences:

The main difference is that if you create a new prefab by dragging from the project tab, the prefab will be created with all it's script variable values at their original settings.

Whereas if you duplicate a instance of a prefab from your scene, and you have script variable values which have been changed in that instance (for example, the move speed of a character), then a duplicate of this existing instance will also take on those changed values, rather than the default prefab values.

Also if you have renamed the instance in your scene, any duplicates of this instance will take on the new name, rather than the original prefab name.