There is an old saying "There is nothing new under heaven" and if we are to believe that then there is no such thing as a unique and original storyline. Which is saddening and daunting and makes many just want to give up. It makes others write predictable story lines that fit in acceptable genres and use this cop-out when challenged. Whether that statement is true or not is irrelevant. What is relevant is that you want to create a story that is unique to you and will be unique to your readers. This does not mean that you cannot or should not be inspired by the things around you. Look at Wicked. We all know the story of The Wizard of Oz, right? It has been redone a dozen times (often badly) and there is no way another hack can give us a unique perspective on a story everyone already knows, yet author Gregory Macguire does exactly that. He did it so well, that he has a booming enterprise of novels from it.
So the key to uniqueness is not necessarily to come up with a story line no one else has EVER come up with, but to look at other story lines and figure out how you can do it better. One of my first screen plays was originally inspired after watching I Know What You Did Last Summer and despising the predictability and simplicity of the story line. Since my story hasn't actually sold yet, I cannot say that it is better; but I sure think it is!
Some of the best story lines come from our own dreams. They are unique to us, but they are influenced by everything we watch, see and do. Keep that in mind as you jot those little dreams down. After I have a particularly vivid dream that I think will make a good story, I will often do research to see what other stories are similar and see the reviews they got. If I have a clear concept for my story and there seems to be a viable market for it; I will hastily write out my first draft, then do some reading on the other stories out there. See what the readers had to say about each book, what their comments were and why. With that in mind, I hit my second draft, crafting it to the desires of my audience.
For example, Science fiction and Fantasy thrillers tend to be a lot more judgmental of plot holes and have a much higher standard of expectation for prose. Criminal thriller readers tend to want detailed educated sounding explanations for procedures, but do not require high prose and tend to be more interested in the plot than the science behind the catching of bad guys. And those who read paranormal do not have as high an expectation for prose, but will totally ream you if there are plot holes or continuity errors! Not that every person who reads any of these categories will necessarily feel this way, but these simply tend to be the trends.
After you do this research, keep this information as it will help you when it is time to get an agent! Knowing your market, what they think, how they feel and what other books are out there in direct competition is a very good way to pitch your sale. It also indicates that you considered those issues when writing your story.
The most important thing to remember: in order to write a unique story you must remain true to yourself. We are all unique individuals and if you let your voice be heard no matter what, the story will be unique!
Now just a quick business note to all my friends. I welcome comments and questions. If there is anything in particular that you have questions about, or even if you disagree with my blogs, please feel free to comment. I am by no means an expert in this field, I am simply giving my perspective and thoughts. Discussion is healthy and other opinions and thoughts are welcome! If you would like to request a topic for me to cover, feel free. I will do my best to oblige.