This question has been brought up a lot, so we've published an article about playing a real guitar Versus playing guitar hero.
Here is an excerpt:
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...This part I, personally, hadn’t anticipated when I took up the guitar as an instrument: calluses. There’s no real way around developing them on your fret hand with a steel-string guitar. Just practicing for a little while initially will leave your finger-tips sore. I assure you, this is perfectly normal. Over time, you’ll develop calluses to help with playing the guitar. This toughening of the skin is essential and makes it much more enjoyable to play as you can comfortably play longer. It means some sticking-it-out but the longer term results of an incredibly portable instrument you can play are very much worth it.
The last part would be maintenance. With Guitar Hero/Rock Band, all someone would have to do is plug/unplug the guitar from the system and change batteries (if you’re using wireless). The real thing does take a bit more than that. These two elements are the most tedious, but they are the core skills every guitar player needs: Stringing a guitar and Tuning it. Anyone with any measure of experience with string instruments will tell you that the instrument being in tune is incredibly important. It ensures sound quality and that you are accurately playing the piece of music. Again, a good deal on a beginner guitar will include a tuner either with or, for acoustic...
For the full article visit:
Guitar/Hero