Patti Forte, Will Forte's real-life mother, played Patti Miller in the premiere episode "Alive in Tucson". Patti Miller was the mother of Phil Miller, and was shown during a flashback on one of Phil's past birthdays. In the show, she was explained to have been killed by the virus.
In season one, episode seven, "She Drives Me Crazy", Carol (Kristen Schaal) is stuck with a cow in her house that won't go down a staircase. The same thing happened on Bob's Burgers (2011) season one, episode three, "Sacred Cow", also starring Schaal.
In season one, episode six, "Some Friggin' Fat Dude", Melissa mentions that The Shawshank Redemption (1994) is her favorite movie. She later mentions The Godfather (1972) is "like my second favorite movie". Those are the top two rated movies in the IMDb top 250 movies of all time.
The trivia items below may give away important plot points.
In season two, Will Ferrell guest starred as Gordon. We later found out that Gail (Mary Steenburgen) dated him in the show. Steenburgen played Ferrell's stepmother in Elf (2003), as well as his mother in Step Brothers (2008).
There's been a recurring gag ever since the beginning of season two, where a famous guest star is brought in and is killed off almost immediately with only one line of dialogue: -Will Ferrell, as Gordon (season two, episode two) died from a heart attack after being scared by Carol. -Jon Hamm, as Daryl (season three, episode one) was shot and killed by Melissa. -Jack Black, as Rear Admiral Roy Billups (season four, episode one) was shot and killed by Pat.
In the season two episode Secret Santa, Mary Steenburgen's character receives The Eliminator car of ZZ Top fame for Christmas. Mary Steenburgen starred in Back To The Future Part III (1990) which featured cameos by the members of ZZ Top as well as a song written specifically for the movie.
Despite the obvious fact of everyone else on earth being dead, and the constant mention of the large numbers of people all the main characters witnessed dying, there are never any dead bodies shown. Presumably the cities and streets would be filled with the corpses of most of the victims of the virus, but none are ever observed. Except when Mike Miller comes to land for the first time and observes a Government body Quarantine Zone!