Seems like Multi-Safari (at least 2.0.4) broke when upgrading to Mac OS X 10.5.1. I get this error:

“You cannot use the application ‘Safari 2.0.4’ with this version of Mac OS X.”

Luckily, I’ve found a workaround. Just launch Safari from the command line (Terminal.app that is) and it should work for you:

/Applications/Safari\ 2.0.4.app/Contents/MacOS/Safari &