It'd take a lot of explaining to make Uryuu the big bad...so much that I wouldn't even know where to begin to make it all work. Because even if Kubo was somehow able to plausibly explain his motivation for faking friendship all this time, he'd need a plausible way to obtain the power worthy of a main antagonist since the Uryuu we know of presently isn't all that strong. And it would be extremely hard to believe he was just intentionally faking his skills and strength this entire time. I'd honestly have an easier time believing Ryuuken could become the main bad guy.
Instead, I'm sure the Ishida's will remain good guys in the end. Afterall, someone's going to need to teach Ichigo how to wield those latent Quincy powers of his.
