How would Shakespeare's audiences have reacted to the play?
To answer this question, we need to have a little bit of context about attitudes toward the supernatural during Shakespeare's time.
King James VI of Scotland believed wholeheartedly in the perils of witchcraft, which led to trials against witches that began in 1591 and ended in 1597. Convinced that he was going to be murdered by a coven, he began to study witchcraft and published a volume of these studies entitled Demonology. When he became the King of England in 1603, this obsession continued. Thus, we can conclude that Shakespeare likely included witchcraft in his play to please the king.
Audiences at this time also shared this belief in (and fear of) the supernatural. When the first witch is offended and with her fellow witches casts a spell as retaliation in Act One, Scene Three, Shakespeare's audience would have recognized this as one of the most common charges brought against witches at the time: "mischief following anger." This, as well of the other scenes involving the witches, would have inspired a great deal of fear, anxiety, and fascination in Shakespearean audiences.
Since we'll never know for certain how the audiences would have acted seeing the play we have to examine the history and cultural norms surrounding the Elizabethan time period.
Most people during this time period did in fact believe in witches so the audience's reaction to the opening scene and subsequent scenes with the witches were, most likely, taken very seriously. The audience would have reacted more emotionally than audiences do today to the witches on stage. They also would have contemplated what was being said by the witches much more closely. The concept of Evil was a very intellectual topic during this time period. The audience would be frightened and intrigued to see Evil manifested physically on stage by the witches.
As mentioned above, the audiences of Shakespeare's time would have taken the threat of witches very seriously. The period between the 1400 - 1700 AD in Europe is known as the classical period for witch hunts and witchcraft trials; marked specifically by the trial of Joan of Arc by the English at the beginning of the period, and the hysteria and trials of the Salem witches in 1692 in New England at the end of the period. Specific laws against witchcraft were passed in England in 1563 during the reign of Elizabeth. Many people of the time had an almost hysterical fear of witches and would have found the witches in Macbeth quite scary rather than somewhat humerous as they are often considered today.