In Shakespeare's Macbeth, what Lady Macbeth underestimates probably isn't the crime of killing a king. What she underestimates is her vulnerability to guilt. She overestimates her ability to resist guilt.
When she plans the assassination, manipulates her husband into taking part, and plays a key role herself she defies traditional gender roles and reveals the reality behind her appearance. Though she plays the gentle hostess when King Duncan arrives at her castle, she is anything but gentle.
After the assassination, she tries to control her husband's "weak" reaction to what they've done and does tell him that washing away the literal blood will eliminate any evidence that they had anything to do with the assassination. Figuratively, of course, the blood that could serve as evidence if they don't wash it away also represents the guilt they feel for shedding Duncan's blood. The symbolic and figurative meaning of the blood becomes clear, of course, during the later hand-washing scene when Lady Macbeth wrings her hands while she is sleepwalking. The effects of guilt on Lady Macbeth are then demonstrated.
At the same time, one might also argue that Lady Macbeth doesn't underestimate her vulnerablity to guilt. In Act I when she prays to her spirits to make her aggressive and merciless like a male warrior, she demonstrates that she is worried that she isn't ruthless enough to do the deed. She continually ridicules her husband for being "weak," but she herself prays to be made "strong." In the end, she and her spirits fail. She falls prey to the traditional, female emotion of pity.
Like life or actuality, Shakespeare's Macbeth is extremely complex, so there exists still another interpretation. Lady Macbeth's mental collapse in Act 5 is probably more the result of the cumulative deaths that have occurred more than just the result of the first assassination. Lady Macbeth never planned to kill Banquo and Macduff's family. Her guilt may not be so much a result of the first assassination, so much as the result of what she has unleashed--a husband who kills on a whim, quickly and easily, without thinking and proper planning: a husband who slaughters an entire family for no good political reason. What she underestimates, then, is her husband's capacity for evil.