Readers should always be at the front of your mind – while marketing, pricing, editing, designing covers, being available online – with the ironic exception of when you’re writing. You can’t worry about whether that book will sell, if fans will like the sequel, what the reviews will be of your novel that touches on a third-rail subject like race or religion… you just have to immerse yourself in the story and write the best damn book you can.
(Upon edits, you can decide if you want to pull back, self-censure, or tailor your book to meet your fans’ expectations. But put your heart into it first.)
The exception to this is if you’re writing to the market, solely to make teh moneyz. Then tailor your story up front, to fit nicely within genre expectations… then forget about readers and still write the best damn book you can. You won’t be happy with anything less.