Originally Jensen Ackles auditioned for the role of Sam Winchester. When Jared Padalecki came in and read for Sam a slight recasting was done. Producers called Jensen and asked if he'd rather use his charm for Dean, saying he was the Han Solo character of the duo and what kid didn't grow up wanting to be Han Solo? Jensen accepted. It became known that he was previously interested in that role, because Dean was funny.
Riverview Hospital, a large mental health facility used as the main set in the season 1 episode Asylum, has also substituted for a prison, a regular hospital, and an apartment building...

There is a particular clock that shows up in almost every episode.
An important aspect of the show's music is classic rock, most of which comes from creator Eric Kripke's own record collection, although one of his paborito bands - Led Zeppelin - has always been too expensive to license.
The role of Ruby was written for Kristen Bell. But she turned it down, Katie Cassidy was cast instead.
Jim Beaver's character (Bobby) was only supposed to make a one-time appearance.
While it maybe coincidental the choice of the name Winchester for the family is interesting. There is a rather famous mansion in California...