The game works fine, but will crash with a "Septerra Core Fatal Panic" if you try to skip any of the quicktime FMV movies. So don't. If you're not getting any FMV movies at all, you might need to reinstall quicktime from the Septerra CD.

The Game works on Windows Vista, but without FMV. Quick Time movie player can't be installed from Septerra Core CD (error message), FMV don't work even if newer version of Quick Time is installed

Those that want to play in XP Service pack 2 or Vista need to head to http://valkyriestudios.com/Septerra/

There are two files you need, first is autosc102.exe.
Second is Septerra104.zip

Runs the 1.02 patch first then extract Septerra104.exe from the second zip into your Septerra Core game folder.

Update your shortcuts to run the game from Septerra104.exe, should be perfect.