According to an alert from Secunia, the issue is rated "highly critical" because of the risk of remote code execution attacks that can lead to complete system takeover.
From the advisory:
The vulnerability is caused due to an error in the handling of parent windows and can result in a function call using an invalid pointer. This can be exploited to execute arbitrary code when a user e.g. visits a specially crafted web page and closes opened pop-up windows.
The vulnerability is confirmed in Safari version 4.0.5 for Windows. Other versions may also be affected, the company warned.