Harry was originally intended to be more serious like his comic book counterpart, but Alan Tudyk was so dazzling in his audition that the character was reimagined to suit his comedic talents.
Deputy Liv was only intended to be a small recurring character, but Elizabeth Bowen had such an immense rapport with Corey Reynolds (Sheriff Mike) that they expanded her role.
In the comics, Harry was addicted to old pulp detective novels. In the show, it was switched to Law & Order (1990) reruns.
The expansive overhead shots that they often play at the beginning of new segments, which show most and sometimes all of the town, set in the midst of the surrounding mountains, are pictures of Telluride, Colorado.
In the comics, Harry is only depicted as an alien, he disguises his identity from those around him using the powers of his mind. It was decided that viewers would be more sympathetic toward a human, but Max (who was loosely based on the comics' little Honey) was created to provide occasional glimpses of Harry in his true alien form.