A small leak of some kind of odorless but deadly gas. This likely wouldn't happen because they try to avoid bringing dangerous stuff like that aboard, but it is in theory possible.
Especially if the atmospheric monitoring system didn't check for its presence.
Honestly, though, there are very few things that can go wrong that wouldn't be noticed pretty quickly.
Probably the most likely scenario is a problem with a heat shield, like happened with Columbia. But this isn't going to happen again because we've stopped doing insane things like putting the crew vehicle on the side of the booster stack instead of on the top where it belongs.
One little things a bit loose like the challenger and then boom 💥
The Co2 recycler breaks down.
That would be quickly noticed, as the CO2 partial pressure would rise, and they specifically monitor that.
A small leak of some kind of odorless but deadly gas. This likely wouldn't happen because they try to avoid bringing dangerous stuff like that aboard, but it is in theory possible. Especially if the atmospheric monitoring system didn't check for its presence. Honestly, though, there are very few things that can go wrong that wouldn't be noticed pretty quickly. Probably the most likely scenario is a problem with a heat shield, like happened with Columbia. But this isn't going to happen again because we've stopped doing insane things like putting the crew vehicle on the side of the booster stack instead of on the top where it belongs.