Factual error: When examining the sand, Bobbi states "According to carbon dating..." Fitz finishes by saying "It's a billion years older than the earth." However, carbon dating is only good at determining the age of something to about 60,000 years old. The only thing carbon dating could tell about the sand is that it is 60,000 years old or older. It certainly couldn't determine that the sand was 5 billion years old.
Continuity mistake: In the opening of episode 20, Coulson meets General Talbot in a saloon that is a secret entrance to their hidden base, a base that is many stories underground. Yet in episode 22 Coulson uses his robot arm to call another jet; it appears outside a window! He can't have a window in his office, if the base is several stories underground. And to verify it isn't a "video window" or "projection screen", Mac throws a chair through it, essentially saying "We are above ground, let's go get in that jet in front of us." (00:19:40)
Continuity mistake: When the Watchdogs destroy the government facility near the start of the episode, 6 shots of Nitramene are fired onto the building's exterior before it implodes. But moments later when Coulson calls Mack, he (Coulson) is watching the news report of the event, and the 6 shots of Nitramene are nowhere to be seen.
Character mistake: Lance and May walk into a bar in Massachusetts. As they enter, the camera pans and shows a large banner on the front window. The banner is advertising "game day" food and drinks. In very large letters the banner shows Boston Red Socks. The actual correct spelling is Boston Red Sox. (00:05:45)