That depends...murdering Duncan is serious bad karma because it disrupts the great chain of being, thus throws the entire natural order out and risks chaos. So from an Elizabethan audience's perspective, the most shocking murder might have been that of the king. It is, after all, high treason. This coupled with Macbeth's own argument against it--Duncan has favored him, he may achieve his ends by chance without his trying, and, finally, he should protect the king from harm, not lay him open to assault--suggests that the ultimate act of wrongdoing is in killing Duncan.
Having said that, Macbeth seems to be most undone by the murder of his friend, his guilt over this is a possible indication that, to his conscience at least, Macbeth feels that killing Banquo was the greater evil. Both Duncan and Banquo are innocents, but though Macbeth is troubled by what he has done to Duncan, he is literally unmanned by what he has done to Banquo. He halucinates, and completely loses control in front of company.
Macbeth's emotional state may be simply the natural consequence of too much stress; or, it may be a sign that he has crossed the line in killing his friend Banquo.