I always carry with a round chambered and my firearm has no safety.
If and when I ever need to use it, it is likely I want to it to go bang as soon as I need it without having to manipulate it.
In a shooting situation certain things typically happen. Flee, fight or freeze. If one is in the two latter conditions, then the high adrenaline rush typically renders fine motor skills diminished.
And while the typical superhero is always calm in shooting situations most people are not and have to be prepared for it.