Probably the fact that you are using a computer program to manipulate pictures, designs etc in a two dimensional medium that does not have an actual light source...and that what we think of as photography is a 3rd dimensionally rendering in that 2 dimensional difference asthetically. For example: You see a lot of people's PS artwork use dropshadow effects. But since they are not thinking in terms of the photographic principles if they do not actually take the photo - they might make the error of causing the shadow to drop in the wrong direction from the way something would cast from a light source in reality. It might not be even something they think about, but to a trained eye it looks horribly unnatural, and can ruin the picture. All effects in photoshop were originally things that were done with a camera, flash, darkroom, or chemical processes by hand. Yet we take this very for granted these days. My answer : It is difficult to use PS without making unnatural effects, the hardest thing is to make PS maniuplations not detectable and therefore effective.