HI,
If you updated to Safari 5 and this started happening after the update, it's possible you have third party Safari add-ons that aren't compatible with Safari 5.
Go here for trouble shooting 3rd party plugins or input managers which might be causing the problem.
Safari: Add-ons may cause Safari to unexpectedly quit or have performance issues
If third party plugins aren't the issue, go to ~/Library/Caches/com.apple.Safari and move the "cache.db" file to the Trash. Relaunch Safari and try File/Save.
If that didn't help, try troubleshooting the Safari .plist file.
Go to the Safari Menu Bar, click Safari/Preferences. Make note of all the preferences under each tab. Quit Safari. Now go to ~/Library/Preferences and move this file com.apple.safari.plist to the Desktop.
Relaunch Safari and see if that makes a difference. If not, move the .plist file back to the Preferences folder. If Safari functions as it should, move that .plist file to the Trash.
And repair disk permissions...
Launch Disk Utility. (Applications/Utilities) Select MacintoshHD in the panel on the left, select the FirstAid tab. Click: Repair Disk Permissions. When it's finished from the Menu Bar, Quit Disk Utility and restart your Mac. If you see a long list of "messages" in the permissions window, it's ok. That can be ignored. As long as you see, "Permissions Repair Complete" when it's finished... you're done. Quit Disk Utility and restart your Mac.
Carolyn 🙂