I love my email Spam folder. Take today's bit of spam - "Life is short. Have an affair." And yes, reading that I laughed out loud. It's all about perspective. As a crime fiction writer and reader I've written and read about affairs ending in murder and death. So I'm reading, "Life is short. Have an affair. Life becomes even shorter."
As a story prompt an affair can work in many different genres from romance to crime. One of my favorite movies is "The End of the Affair" with Julianna Moore from 1999 which is based on the Graham Greene novel of the same name. This story takes a look at guilt, and jealousy, and redemption stemming from the affair and its sudden end. No murder. So you can write about an affair that doesn't reduce itself totally to an act of violence.
Writing great stories that strike a cord is more about blurring the lines than sticking with a variation of what's already been done. And yes, that's hard to do but when you can, you know you've written something special.