1. True Lovers: We all want to be loved deeply and passionately, to believe that we are the only ones they could ever love, even if it isn't technically true. We want a lover that is willing to die for us, or to profess to be willing to die for us, or at least have our backs. We all want to be valued and praised and held high. Grand passion fueled all the major love stories: Romeo and Juliet, Tristan and Isolde, Love Story by Erich Segal and the dubious entry, Twilight. This example proves that no matter how badly structured or how annoying the characters, a book that taps into universal wish fulfillment can transcend the genre it targets. The thing modern writers so often fail to understand is that random hooking up is not deep, abiding passion. If the object of your affection can toss you off the bus at any stop, you aren't valuable. That is the opposite of the wish.
2. The Abused Victim: Consider Stieg Larsson's Dragon Tattoo trilogy. Why did so many people love the books? They were not well constructed. They had plot holes galore: info dumps, redundant reveals, and muddy plot lines. They had brutal and explicit scenes that turned some readers off. Yet they sold like hotcakes and spawned two movie versions. The success lies with the abused character Salander. She was mistreated as child and abused as a woman. We love watching the hacker-girl (tattooed and pierced and slightly sociopathic) fight the system. She gets vicious, whacked out revenge and takes back her power. This theme still plays well in modern society. It could be set in 1800 England or 2010 New York. It is closely related to the underdog theme.
3. The Underdog: We love seeing the little guy prove everyone wrong. I think most people have felt like the little guy at some point in their lives. We love watching someone go from rags to riches, proving to the rich people, or the talented people, or the beautiful people that their assumptions were wrong. The story line tears down the artifice of the people on the top and shows that they aren't as happy, glamorous, or successful as they appear to be. It is human nature to wish for that to be true. To believe that the average person isn't missing out on anything that other people have. It so often proves to be true. The glamorous life isn't that glamorous. Money can't buy happiness and you shouldn't judge a man or woman by her clothes or financial status. We also love to tear down what we've built up. There's nothing like seeing someone that we've elevated fall off their pedestal. This covers everything from Bad News Bears and We Are The Titans to Forest Gump.
4. The Secret: Curious people dislike unanswered questions. They will hunt and probe until they've answered them. They build up huge conspiracy theories when the answers aren't available. The flip side is that people like to keep secrets. Shame or fear motivates them to do everything possible to keep the cat from leaving the bag. This is the broad appeal of Mysteries and Thrillers. We like piecing the clues together. We want super-smart sleuths out there solving crimes for us. We want a white knight in a blue uniform to catch the killer and find the missing child. We want to believe that justice will be served, because it so often fails in real life. In fiction, the criminal is convicted and made to pay. This is the appeal of everything from Columbo to Sherlock Holmes to The Night Stalker. It is also the appeal behind vigilante stories. If the proper channels can't solve it, the everyman hero will do it for them.
There is a saying that there aren't any new stories; there are only new ways to tell a story. I would expand that to say there are only a few universal themes. The unique way you play with universal theme will give you the best chance of having a mega best seller. It helps if you write it well.