Say that you fell off your chair after your daily AV scan turns the UI to blood red. Then you think that can't possibly be the case. What do you do before you let the file out of quarantine?
I have my antivirus configured to prompt me to let me choose what action to take whenever a threat is found. Because of this nothing ever gets quarantined automatically. I've been cleaning malware from PCs for 26 years and (usually) I can quite easily tell if something detected is an actual threat or a false positive. If you're ever unsure about a file then it's worth checking it at VirusTotal to see if it's safe or not.
That's what I do, even with large programs/games. I did this with the MOD "Goldeneye Source" before installing it for real.