Impossible is difficult, but doable. There's one area in level 9 that was ridiculous (the containment-locked hallway onboard the Valor) and I needed to use the Line Gun to get past it. Otherwise, one gun on Impossible is very doable.
Edit-- oh yeah, and f**k that "Don't get cocky" achievement. I only got it recently, and it was a motherf**king pain in the ass.