I have Rocksmith installed on two devices, one a laptop and one a pc.  The pc is a much stronger machine then the laptop.  I am having a few issues with the sound on the laptop, but I have noticed that any changes that I make in the profile follow to the other device such as when I change the head stock from 3 + 3 to the 6 it changes it on the other.  I use one guitar upstairs and two others down stairs.  All three of them are different.  One is a Strat, one is a Les Paul and another is a Dean.  I think all three have suttle differences in their output and my guitar volume tends to differ.  Is there a way to keep the setup profile from changing from one device to the other?  I would like to keep the strat setup on the pc and the other two on the laptop.  Or do I need to do the calibration each time?  Will a second profile make a difference?

Go in your steam library, right click on RS2014, go to properties. In the Update tabs, unselect the steam cloud sync so that your profile isn't sync between both of your computers.

 

The downside is that your score/pourcentages won't be sync on both of your PC but i think it's better than having to change your settings everytime.

I would calibrate every time you change guitar, there can be quite a difference in output levels.  You do know the quick way?  Just hit enter at the tuning screen (it makes you tune every time you switch the game on anyway) and bam, done in 30 seconds.