Beam Me Up, Scotty!: Sagan says "billions" with a strong "B" many times on this show, but he never utters the phrase "Billions and billions." That came from an affectionate parody of Sagan done by Johnny Carson on The Tonight Show. Word of God has it that he found it annoying at first, but got over it. And the whole reason he said "billions" with a strong "B" was to emphasize that it wasn't millions, but three whole orders of magnitude greater. He lampshaded and did say the phrase years later in the prologue of his last book, mostly just to be able to say he actually said it. "So just for the record, Billions and Billions." He made it an Ascended Meme when he named the book Billions and Billions: Thoughts on Life and Death at the Brink of the Millennium. (Despite the parody, Sagan was a regular guest on the Tonight Show, and may have uttered the phrase during one of his appearances, too.)
Tyson drops "Billions and billions" in the episode "Hiding in the light" pointing out that zero is useful when you write billions.
Defictionalization: The Mars rovers that Sagan spoke of in Episode 5, "Blues for a Red Planet", were defictionalized 23 years later with the highly successful Spirit and Opportunity rovers, and later the Curiosity rover. Also, the spacecraft Cassini did eventually reach Saturn and is exploring the system to this day, and its Huygens lander did successfully reach and photograph the surface of Titan, as Sagan had hoped.
In episode 9 Amanda Seyfried does Marie Tharp, one of the first cartographers of the ocean floor.
Playing Against Type: Most people would not normally associate Seth MacFarlane, he of Family Guy fame, with a science documentary. And even he says he's the least important person involved. And yet without him, the series likely would not have happened. And Ann Druyan has noted that Seth and Carl would have gotten along quite well.