It is all about timing and also, on the higher difficulties, batsman confidence.
If your batsman is new to the crease and his orange line is not nearly full it will be very hard to hit sixes. This has most effect on hard mode, but has a little effect on medium.
The only back foot shot I've managed to hit a six with is the hook and pull. Front foot shots like the on drive and cover drive are easy to hit sixes with, and also leg glance. Square drive is a little bit harder.
Just practice the timing until it becomes second nature, but the moment this happens the game will become very easy.