I can't seem to find the video of it anymore, but at a talk back in (I believe) 2012, STS-135 commander Chris Ferguson described a story from one of his last mission simulator runs.
For this particular sim, his crew went behind his back and coordinated with the SimSups to find out everything that was going to be thrown at them ahead of time. Throughout the sim, he remarked at how well his crew was able to rapidly respond to all the anomalies thrown their way.
Where it came to a head, however, was when they simulated their final approach and landing. The simulation called for a last minute communication dropout due to a fire at the since-closed Merritt Island Spaceflight Tracking and Data Network station, commonly known as MILA (Merritt Island Launch Annex). Within the simulation, it was only possible to indicate this to the crew as a loss in communication -- the out-the-window view wasn't able to show anything.
As Pilot Doug Hurley was piloting the simulated Atlantis around the Heading Alignment Cone, however, he looked out the window to his right and said, "Huh, MILA's on fire!"
Commander Ferguson was caught on the simulator cameras looking out the window, only to see exactly what the simulator was able to produce -- nothing out of the ordinary.
It was only after wheels stop that communication with MCC was reestablished, in which they confirmed a fire at MILA, completing the joke.
This sim run was famous enough that it earned a place on the post-flight hall decorations.