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Depends on the look you you are going for.

My enemies are 128 pixel high and all the Textures for the Tiles are 256x256. To get more of a DOOM look.

You can use any Software you like. I use Blender to model the enemies in 3D and render them in a small resolution. But you can use anything from Gimp to Photoshop. As long it can save the Pictures as PNG.