I don't like having to remember to hold differently for different rifles, preferring the bullet to go exactly where aimed.
The reason I don't like 6 O'clock holds was born out to me a year or two ago when clearing a property of Buff.
A Bull Buffalo jumped in front of us and took off across our front flat out to get away across the flood plain. I swung onto it at about 90 yards and dropped it with a head shot. In the heat of the moment, I very much doubt I would have been able to quickly lift the gun up, swing onto it, and through it (for the right lead) and shoot it.
That was with a 318 WR and open sights.
Any time I have to think seriously before shooting like a different hold, different bullet etc, it takes the enjoyment and spontinaity out of it and you can lose it.