I haven`t tried Paint.NET but there are a (very) few programs that insist on changing the format of the image when you do a save.
I have Paint.NET on one of my systems and have just tried it with TgaTool. For its own wierd reasons Paint.NET insists on saving all BMP images in 32 bit format. This is no good for tgatool as the data it passes over is 24 bit for the main image or 8 bit greyscale for the alpha and this is what it expects to get back after edits. This means that when you edit either part it will seem to be displaying in Tgatool2 ok (because this uses a simple BmpLoad to display) but when saving or exporting it will read the data wrong and create a distorted combined image.
I have Paint.NET 2.1 (Beta) and it doesn`t seem to have any settings to change the way it saves. And although it does seem to have support for layers and alpha channels it doesn`t have direct support for Targa. Shame really as it is quite a nice paint program (and free)
