I regularly have the chance to do some flying in a real level D 767 sim. The first time I did this was when I had about 250 hours as PPL on Cessna's. To put short, I was not able to land the beast back then, even I did know the aircraft systems very well (e.g. no problem to program the FMC etc).
During takeoff I was kinda surprised about the effort needed to stay on centreline at those faster speeds, maybe also because of the acceleration feeling that you don't have in small planes. During landing I was way too slow with throttle adjustments, so I stalled it at 1000ft. An airliner needs more energy management and reacting before things happen.
The second time I put it down quite well, but when A real pilot faints and the stewardess asks you to fly it, you only get 1 chance.