The hardest part of the transition from RHS to LHS is the mental transition and the longer you have been in the RHS the harder it will be. Have seen many a fine fellow begin to come unstuck in the SIM when things start going wrong and he/she realises that everyone is looking at them for the answers, possibly the first time any real associated pressure has been felt. Now add all the points made above about fuel policy and planning, MEL, weather minima, (and how to calculate them), etc. etc. When I got my first jet command the CP said, "From here on you will find that most FOs will fly better than you, you now have a whole load of other things to consider, not just the menu!"
The actual flying is the same as before, just a different seat.