Astronauts typically have one chance to complete a process or effect a repair--like landing a lunar module or replacing the optics on the Hubble Space Telescope)--and in a tight window of time. Simulation is the only effective means to be well practiced in such skills before attempting them for real.
Astronauts are subject to extreme conditions and disorienting effects like weightlessness, high G-forces and prolonged confinement in extremely tight quarters.
Astronauts train for weightlessness and extra-vehicular activities (EVAs) underwater, in a Neutral-Buoyancy Laboratory (NBL).
Simulation is also essential for ground crews; flight control teams practiced numerous simulations (largely improvised) in rescuing the Apollo 13 astronauts when the spacecraft became crippled.
Failure during simulation is far less costly (and disastrous) than aborting a mission; this is true of all simulation training, for example, in air traffic control.