Various things that I've heard (https://tvtropes.org/pmwiki/pmwiki.php/TroubledProduction/LiveActionTV) include: The combination of Cybill Shepherd's and Bruce Willis' gigantic dueling egos, Cybill's pregnancy, Glenn Gordon Caron's nonsense, Bruce's post-Die Hard movie success, the mangling (https://web.archive.org/web/20061031125239/http://www.jumptheshark.com/m/moonlighting.htm) of Dave and Maddie getting together

IMO, the same thing that ultimately destroyed Castle. The lead's couldn't stand each other. In later seasons, they put a limit on the number of scenes they would film together. They obviously used stand-ins for a lot of scenes so the leads wouldn't have to film together.

When you are trying to make a romantic dramedy and leads don't want to film together, it's a problem.