Can I run Rocksmith on a late 2006 imac 6.1 by changing the drive?

Why would you need to change the drive? Replacing a drive in an iMac is not a trivial project. You must disassemble the computer almost completely. This includes removing the display screen. I would look for some disassembly tutorials to be sure you can perform the task. Should you need it be aware that no Apple shop will service it once you've opened it.