To people who grew to like and/or relate to Marion while considering her the main character of the movie, the sight of her lifeless body lying on the bathroom floor after the shower scene. It also looks almost like she sheds a Single Tear right before she completely dies.
Apart from his mother's domination inside his brain which forces him to kill most of the women he is attracted to, Norman gets quite a big amount of bad luck with them, be it the chain of reactions leading to the death of Mary in Psycho II or the death of Maureen in Psycho III.
Norman begging Mary not to let "them take me back to the institution" and recalling memories of his mother caring for him when he was sick before she went crazy in Psycho II
Seeing Norman's childhood in Psycho IV:The Beginning is painful. It's hard to imagine living with Norma Bates and not losing your mind.
Norman fearing that his unborn child could turn out as crazy as he did.
His first victim was a teenage girl who had the hots for him, and a beautiful grown woman.