Here are a few registry hacks I find useful. I’m posting this mostly for my own reference when setting up new Windows 8 + Visual Studio 2012 machines.

Always launch new instances of desktop apps
There is nothing more annoying than when I try to open a new command prompt or Notepad and the immersive launcher (“start screen”) decides to activate my existing instance. Thank you launcher, that’s exactly what I wanted. Not.
Create a DWORD value at HKEY_CURRENT_USER\Software\Microsoft\Windows\CurrentVersion\ImmersiveShell\Launcher named DesktopAppsAlwaysLaunchNewInstance with value 1 and Launcher will never try to be “helpful” again.

GET RID OF ALL CAPS MENUS IN VISUAL STUDIO
Do your eyes a favor and set the DWORD at HKEY_CURRENT_USER\Software\Microsoft\VisualStudio\11.0\General named SuppressUppercaseConversion to 1.

Prevent corners from capturing the mouse on multimon setups
With multiple monitors, more often than not my mouse gets captured in the corners because shell thinks I would like to use the charms bar. I never use the charms bar on my desktop, hence this is more annoying than useful. Thanks, but no thanks. Setting the string at HKEY_CURRENT_USER\Control Panel\Desktop named MouseCornerClipLength to 0 fixes this.

And I have one more non-registry efficiency improvement tip. Since the metro apps for Music/Videos/Pictures are pretty much useless on desktop but Windows defaults to using them for all music/video/picture formats, uninstall them. You will save yourself the trouble of changing the associations for every single file format supported by them and having a perfectly fine desktop alternative.