The red frog that keeps appearing here and there through the series comes from the first scene of the pilot. It is, depending on who you ask, the first "person" to die, the first reaper, or both. The frog is an Argentinian horned frog (aka, "the Pac-Man frog"), which does not make sounds like North American frogs (during one take, however, the frog hissed when Ellen picked it up, scaring the daylights out of Callum Blue and Jasmine Guy), The "frog sound effect" is dubbed in. The Pac-Man frog also has sharp teeth, and should only be handled by professionals, as its bite is very painful.
While Rube's cause of death is never outwardly stated, several of the second season episodes hint that on the night he was killed, Rube tried to rob a bank (the wanted poster Rube finds when searching for information about Rosie, and the gun he's constantly carrying around in his flashbacks).
According to Bryan Fuller (the show's creator and head writer for the first four episodes), it was originally planned that George's father would be gay, and this development would spell the end of Clancy and Joy's marriage. After Fuller left the show, the show's new executives decided that Clancy should be heterosexual, but philandering with his female students.
According to Bryan Fuller, among his problems with the network was that they argue Rebecca Gayheart wasn't pretty enough, to which Fuller replied that she was a supermodel. After the creator left the show, Gayheart's character was written off.
The set location for the Lass Household, 3851 Osler Street, Vancouver, BC (depicted as "3851 Beatrice Lane" in the series) was the location of an actual murder in 1924. The murder victim was a young woman named Janet Smith, and her accused murderer, a Chinese immigrant, who was subsequently acquitted, ignited racist feelings and legislation against Asians. The murder dominated the headlines of the Vancouver Sun for weeks. Also, the BC Historical Federation, Volume 43 No. 4, has a picture of the house on its cover (PDF link at Google).
Although set in Seattle, the series is actually filmed in Vancouver, B.C., Canada. No effort is made to hide street signs, local business names (e.g., Avalon Dairies), etc., and in one episode both a Canadian flag and a B.C. flag are visible in the background.