I play both real guitar and rockband guitar (expert). There's nothing similar about them, and there's nothing about my real ability which would hinder my "fake" ability. In fact, the ability to control finger positioning only helps with the plastic strat.

A professional musician would find rockband rubbish I'm sure, and may even have a hard time playing the game, but it's not because he/she is a professional musician, it's because they suck at videogames and/or haven't put the time in to learn the game.

Properly calibrated, there is no noticeable lag. Sure, there's likely some microscopic latency issue regarding the speed in which the signal travels from guitar to xbox to screen, but nothing the eye/mind will notice and certainly nothing which would cause the issues as FnR states.