I am speaking, of course, of the ill-fortuned Megara. (Literal answer is fine, although I'd welcome commentary and analysis. Ideally, links will come from Academic sources where possible.)
Hera struck him with madness, and he killed his wife Megara and children. In some myths, his need to atone for this led to him performing 12 Labours of Hercules. Two plays, by Euripides and Seneca, have a different storyline:
In the works of Euripides and Seneca, a usurper named Lycus has taken the throne of Thebes in Hercules' absence, killed King Creon, and is now forcing marriage on Megara. The tension of the plays comes from the characters hoping Hercules will arrive in time to save them from Lycus and his schemes. When Hercules finally comes home, he defeats and kills Lycus and then gives thanks to the gods for his timely arrival and the safety of his family. As he is praying, however, he is struck by Hera with a madness in which he believes his sons are those of Lycus and that Megara is his adversary Hera, and he kills them all. The plays both end with Hercules in suicidal remorse at his deeds and his cousin Theseus helping him deal with his grief.
The pre-Euripides storyline has Hercules and Megara living happily in Thebes, when Hera causes Hercules to go mad and attack his family. Hera's vindictiveness towards Hercules went back to his birth, as he was one of Zeus' many children by other women, and she persecuted him throughout his life.