To cause one to be continually unhappy; to be a great and continuous source of stress for one. For some reason, the new manager seems to have decided to make life miserable for me. Don't worry, we'll make life miserable for them is they refuse to sign the contract.

To cause oneself a great amount of stress, anxiety, sadness, etc. I don't understand why she keeps making herself miserable in a job she hates. She's just not interested in you romantically, Jack, so stop making yourself miserable pining over her!

Extremely unhappy, depressed, or wretched. Everyone just stood around looking miserable as sin during the ceremony. I felt as miserable as sin because of the breakup, but I was going to be best man at my brother's wedding, so I had to pick myself up and dust myself off.

Extremely visually displeasing or unattractive. This old car is all beat up and ugly as sin, but it's still going strong after all these years. I'm sure I looked as ugly as sin by that point, with my makeup smeared all over the place and my hair a total mess.