A generation apart
You have to see these aircraft as a developement generation apart, the Spitfire is a thirtys aircraft with no attention paid to ergonomics or crew comfort (drop your map and it is the last you will see of it for the rest of the flight!)
The Mustang is an aircraft that takes the develpment a stage further, sit in it and you will see an aircraft that feels "modern" (drop the map and just pick it up off the floor!) all the controls are much better placed and on the whole it is a much better working enviroment.
The Spitfire is a much better point defence fighter with a lower wing loading, better rate of climb & it will turn tighter. It wont go very far!
The Mustang will fly much further and take the fight to the enemy but it is not best equiped for point defence due to the ROC.
The Spitfire is probably less hard to fly, I have been told that a few hours flying the Chipmunk from the rear seat will teach you to fly the Spitfire, the Mustang is altogeter a little "hotter" to fly.
Both are true classic aircraft and I dont have the words to describe my trip in the back of a Mustang apart from remembering the mind blowing power.
Interestingly one of the American unlimited air racers who was using a much modified Mustang, got him self a Sea Fury and found that all the "tweeks" he had done to make the Mustang faster were installed on the Sea Fury as standard! But then the Sea Fury was a further generation of piston engine fighter development.