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Source: https://writers.stackexchange.com/a/27370
License name: CC BY-SA 3.0
License URL: https://creativecommons.org/licenses/by-sa/3.0/

Several comments have made reference to the squick factor associated with sibling incest. Certainly that would be an accepted reason why your two main characters would not have any interest in one another. But since you want to potentially explore that relationship downstream...

If your two characters have known each other since childhood, there will be reverse sexual imprinting due to the [Westermarck Effect](https://en.wikipedia.org/wiki/Westermarck_effect). It appears to be sufficient for them to have grown up together in the same house -- perhaps one is an orphan? This allows you to build -- at least initially -- a Kim Possible/Ron Stoppable friendship.

Over time, however, your readers will probably [ship your main characters](https://www.theatlantic.com/entertainment/archive/2014/12/shipping-and-the-enduring-appeal-of-rooting-for-love/383954/) if they like them enough. This is good, because it gives you opportunity to build conflict. Specifically, you can leverage the [Childhood Friend Romance](http://tvtropes.org/pmwiki/pmwiki.php/Main/ChildhoodFriendRomance) trope to set expectations.

Consider, for example, if Ron grows up and [gets married to an amazing woman](http://tvtropes.org/pmwiki/pmwiki.php/Main/AuthorAppeal). Suddenly, Ron [becomes desirable](https://www.psychologytoday.com/blog/apologies-freud/201210/why-women-want-married-men), and Kim realizes what she lost. But she's ethical, and Mrs. Stoppable is also her friend. This is a powerful internal conflict. And if you ever decide to kill off Ron's wife, and Kim decides to pursue that long-deferred relationship, suddenly she can realize that it never would have worked after all.

Keep in mind, this is a long-cycle character arc. In book 1, they are friends, and Ron is a dork. In book 2, he's still a dork, and Kim is happy he met Anne. In book 3, Ron gets married to Anne, and the friendship continues. It's not until book 4 that she regrets losing out on Ron -- this is where you kill Anne, and her guilty feelings drive the plot. And in book 5 Ron has sufficiently recovered from his grief to consider Kim as an option.

Original score: 3