Plot hole: Bullets, which have been passing harmlessly through Nick for two whole seasons, suddenly do him great injury here. And though he's taken to surgery, the bullet lodged in his head is never removed. It's still there on the latest x-ray when LaCroix arrives to "consult" with the doctor. (00:00:05)
Plot hole: When LaCroix arrives at the amnesiac Nick's loft, Nick recognizes him as "the doctor from the hospital." But Nick was still comatose when LaCroix posed as a doctor and came to his room, so he shouldn't remember that particular "doctor." (00:19:45)
Plot hole: Because he has no discernible vital signs, the wounded Nick is declared dead in the hospital. When he revives, he's rushed into surgery, where he'd surely have been reattached to a monitor. Somehow, though, no one on the medical staff notices that their patient still has no normal pulse or heartbeat. (00:05:05)
Answer: Nick was sick and tired of being an immortal bloodsucker. He wanted to be human, fall in love, get married, have children, grow old and die. As for Janette, according to her, she fell in love and the passion she felt "cured" her of her blood lust.