Simulation is just that. The most pesky problems can not be found with simulation. The more of your design you simulate (peripherals, analog components, ADC and DAC, etc), the more the simulation will drift away from the real world. I abandoned simulation a long while ago since most of the requests I got was of the nature "I do not understand why it does not work, it runs fine in the simulator". After I invested in some ICEs, I became capable of solving such problems in a fairly rapid manner.

Erik