This is an anecdotal answer, so I'm sorry if it doesn't really fit the site but in my opinion, there's one thing that no simulator, no matter how good, can prepare you for: The emotions you'll feel.
No matter how realistic the graphics are, no matter whether it's got full motion capability and no matter how good the flight model is - until you've taken on that responsibility you just won't know how well you're going to commit.
Like many people here, I spent a lot of my time in flight simulators - afterall, they're a lot cheaper than the real thing. But, never once, have I broken into a cold sweat. Never once have I had one of those moments where I just wanted to be on the ground, having completely utterly forgotten everything I've ever learned.
People focus on a lot of the technicalities, but the truth is I've always felt pretty at home in a cockpit. Moving away from big planes, your average GA plane is not hard to get off the ground- checklists are easily memorized and for the most part you can fly just fine without touching too much. And, I suspect if you've got enough sim experience you could conceivably pull off a circuit - the real, question though, is when you're sat there all by yourself at 1000', sweating, are you going to have the confidence in yourself to fly that plane back down to the ground knowing full well if you screw it up you may not be going home. And what about a stall - when you're sat there, and it's all on you are you going to have that confidence to point the nose down when all you want to do is go up! And, back to the big toys, maybe you're about to kill several hundred people.