A few weeks ago I tried out the You Rock guitar in Pro mode on Rock Band 3, but I only had an hour or so, just to prove it worked and get a taste. I did one quick lesson and then got right into playing, and didn't do that well.
A few days ago I decided to give it another try, having a few hours to really do lessons. However, try as I might, I couldn't get the guitar into the Rock Band pro mode. In fact, the control panel was totally non-functional. I could change sounds with the plus and minus buttons, and play as a real guitar, but nothing else. I tried everything I could think of but eventually had to submit a trouble ticket. To my surprise, they were able to solve the problem easily: I just had to unclick and reclick the neck. I've had to do this a few times since (seems like something about the MIDI connection and Rock Band Pro mode makes the neck electronics get confused periodically -- hopefully they'll fix this in a future firmware update) but never in the middle of a song.
I went through all the basic lessons. This is definitely a lot more of a learning curve than anything, even drums, has been before in Rock Band. And I already know I've barely started, because I tried playing a song on Medium and there were whole sets of symbols and techniques I haven't even seen yet. Even though I have learned some guitar before (admittely 25 years ago), I had more trouble finding the right string to finger and pluck than I had finding the right fret. But over the course of about an hour, I was able to get through the basic lessons and then play a few songs on Easy mode successfully.
In actually playing songs, the one thing that I find hardest about the Rock Band interface is that, if you're holding your hand at frets 1 to 5, and there's a change coming that needs you to be playing frets 7 to 11, the only warning is when that first 7 comes down at you. This is actually harder than playing normally because your eyes are on the screen, so you can't really glance over at the neck to position your fingers. What would be nice is if, scrolling down the screen, there was a little advance warning when you needed to change your fingering position. This would help make up for the disadvantage of having to look at the screen instead of the guitar. (In fact, that question of where your eyes are is a lot of why I had trouble finding the right string, too. Maybe I need to sit at a right angle to the TV so the neck of the guitar is in the same field of vision as the screen.)
Drums still remain my favorite instrument for Rock Band, and I'm still idly thinking of getting a MIDI drum set (so I can have better response and reliability, particularly with the kick drum, and since my drum kit is starting to have some trouble with the snare drum cover bubbling a little bit). I just wish I had more time so I could do all of it.