As-of Paint.NET 3.5.2. This information is not official and some parts may be slightly inaccurate.
Non plugin authors often don't know what is and isn't possible when writing plugins - so hopefully this should be helpful to users wishing to suggest plugins.
Effects can only access the current layer.
Effects can only access the current image.
Effects cannot know or change the blend mode or transparency of a layer.
Effects can blend two images using transparency and blend modes.