There's only one secret to mastering Paint.Net.
Put everything in a separate layer.
For example:
- Every part of a drawing/diagram should have its own layer.
- Before applying an effect to a layer -- clone the layer, and hide the original.
Get very comfortable with all the layer related features:
- New layer
- Clone layer
- Delete layer
- Move Layer Up
- Move Layer Down
- Edit the transparency of a layer
- Switch a layer on/off
- Paste in to new layer
Save the file as a .pdn file, and export copies as .png.