Also, the "Always Use Best Attack" option can help. Each weapon type requires a certain movement or approach for best effect. I forget now which is which, but for example, moving forward would help with a sword, where moving sideways would help with an Axe or something like that. I turned that option on a long time ago and never unchecked it. Which is why I can't remember the helpful movements.
And, yes, Fatigue is needed to do just about anything in this game, even picking locks is harder if your fatigued. This is one of the last games where character stats matter more so than player skills, to the point that other than turning off Always Use Best Attack, player skill has little to do with outcomes.