In Shakespeare's Macbeth, the tragic hero, Macbeth, commits many murders. At first he struggles with the act, but believes that he will get better at it with more experience. This does seem to be the case.
It is a matter of opinion as to whose murder is the worst. In my mind, it is the death of Duncan.
There are several reasons for this. In terms of Elizabethan times, in which Shakespeare lived, there was something called the Chain of Being. The people believed that everyone lived where God placed him or her—this indicated how important someone was. For instance, God was at the top; next came the angels. The next person down was the king; after that there would be other noblemen and women, and peasants would be at the bottom. (There were "chains" of this kind with flowers—the rose was the most important; with metals—gold was at the top; and, even animals—the lion really was the "king of the forest.") Therefore, killing a king was defying God himself and considered a mortal sin for which one would lose his immortal soul.
Macbeth is, at the start of the play, an honorable, valiant soldier for the King. And the King has acknowledged his service and rewarded him. Macbeth admits that he has no reason to kill Duncan except for his tragic flaw: "vaulting" ambition—ambition that drives him beyond reasonable thought.
Duncan is also Macbeth's cousin and friend. Macbeth loves Duncan, and Duncan loves and trusts Macbeth.
The last reason this murder is the worst in my mind is that Macbeth breaks the law of hospitality. For hundreds of years, it was accepted behavior that should your worst enemy come to stay under your roof, you were honor-bound to protect him or her, no matter what was said or done. If a man did otherwise, it showed him—in his defiance of this cultural norm—to be the lowest kind of person: one without honor, dignity or character. This is what Macbeth becomes.
It is important to note that Macbeth has his misgivings. He tells his wife that he does not want to go through with the plan. He says he wants to enjoy the honors that Duncan has bestowed upon him, and how nice it is that his peers think well of him: he doesn't want to throw these things away.
We will proceed no further in this business:
He hath honor'd me of late, and I have bought (35)
Golden opinions from all sorts of people,
Which would be worn now in their newest gloss,
Not cast aside so soon. (I.vii.34-37)
However, Lady Macbeth wants to be the queen and badgers and insults Macbeth until he agrees.