I understand what 'On the fly' does, and I have re-read https://docs.qgis.org/2.6/en/docs/training_manual/vector_analysis/reproject_transform.html
I tend to have it turned on all the time, but I don't know if that is correct or not? I am aware it can cause issues.
I have had a look through the related questions and they all tend to be when users are having problems, and further complicated by people asking about their particular datasets and respective CRS's.
Is there simple rule-of-thumb answer to when to have 'On the fly' turned on and when should it be turned off?