If its powered on, and if the drive is in use, vmware won't let you delete it. I'd make sure you have a good backup, but you can delete it. Another thing you may want to do to be sure is run a script like this

Orphaned files and folders - Spring cleaning - LucD notes

This will find any file that is not associated with a VM and tell you the location. If it shows up in that list its safe to delete, again to cover your self I'd make sure you have backups of anything you are going to delete.