Regions
If you are using Spine Professional and using meshes, we recommend leaving Strip Whitespace OFF.
Whitespace stripping causes problems with mesh UV coordinates.
The best practice is to pre-trim your images before starting to set up your skeleton in Spine.

Pages
Power of two and Square used to be requirements when you have PVRTC compressed images and intend to target iOS.
It's not clear if this is still the case, but by default, Spine-Unity will set your image settings to uncompressed (this means uncompressed at runtime) on import so it comes out clean.

Output
For beginners, and quick testing, leave Premultiply Alpha on. This is compatible with the bundled default Spine/Skeleton shader. This also allows it to be compatible with per-slot additive blending.

If you want to use Sprites/Default or Sprites/Diffuse, leave Premultiply Alpha unchecked and Bleed checked.

If you are using specialized shaders, you should know if it uses Straight alpha or Premultiplied alpha blending and check or uncheck this box accordingly. If you turn Premultiply Alpha off, you probably want to check Bleed.

If you plan to implement custom shaders, using Straight Alpha (Premultiply Alpha off) will likely make them easier to implement.

For more info, check this thread: Premultiply Alpha

Options
Unity does not recognize custom file types even if they are plain text, so we recommend setting the extension to .atlas.txt.
For the most part, The Spine-Unity importer will detect .atlas files and automatically rename them to .atlas.txt for you. But to save it a step and prevent any mixups when updating assets, set the Atlas extension specifically to this.

You can track it here: Warning when whitespace stripping with meshes · #7 · EsotericSoftware/spine-editor

It's likely several months out and what specific behavior it takes is still undetermined, so I recommend you don't count on it working immediately.