SPOILER: Several references throughout his appearances on the series point toward the character Rufus Turner (played by Steven Williams) being Jewish. He makes jokes about Hanukkah and keeping kosher, and most significantly, when he dies, the Winchester brothers and Bobby give him a funeral in a Jewish cemetery and discuss his level of Jewish ritual observance (or lack thereof). Although the funerals for previous hunters had included a ceremonial funeral pyre, the show makes a point of showing that Rufus gets buried without cremation (since cremation is against Jewish tradition).
Unusual for a male-lead fantasy series, most of the viewer demographic are females.
SPOILER: 'Genevieve Cortese' was cast as the character Ruby for the fourth season (replacing Katie Cassidy), and her character eventually becomes romantically involved with Sam (Jared Padalecki). In their real lives, Cortese and Padalecki also became romantically involved, and after they married in 2010, she changed her last name to "Padalecki" both personally and professionally.
The fourth season is dedicated to Kim Manners, a longtime executive producer and sometime director for the show (as well as for past TV shows such as _"The X-Files" (1993)_) who died in January 2009.
Both 'Jarred Padalecki' and Jensen Ackles auditioned for the role of Superman/Clark Kent in some form. Padalecki was a finalist for director McG's reboot while Ackles was the second choice to play a young Clark Kent in the show Smallville.