Safari Locked, Not Responding, Most of Items not Reacheable

Have you tried reopening Safari with the shift key held down?

You may  have adware/malware installed. Try downloading this program which was written by Thomas R, a long time poster. The program will search for malware/adware. The program will do the work for you which makes it easy. It may be necessary to run more than one scan. After running the scans, restart the computer.

Malwarebytes Anti-Malware for Mac      10.10 and later

Malwarebytes uninstall

Try setting up another admin user account to see if the same problem continues. Please post back on whether or not this worked. Also try the Safe Mode. Please post back on whether or not this worked.

Isolating an issue by using another user account 

Safe Mode - About

If it works in the Safe Mode, try running this program when booted normally and then copy and paste the output in a reply. The program was created by Etresoft, a frequent contributor.  Please use copy and paste as screen shots can be hard to read. Click “Share Report” button in the toolbar, select “Copy to Clipboard” and then paste into a reply. This will show what is running on your computer. No personal information is shown. If the log won’t post, try posting it in Pastebin and provide a link in a reply        Pastebin

Etrecheck – System Information

I'm having this same issue. It just started today for no apparent reason. There is a message that pops up when I first open Safari but it goes away too quickly to read. Then I have a window that I can't close, if I click anywhere within it I get an error sound and have to force-quit the program. Nearly all of the menu is greyed out, in particular the preferences option. Basically nothing that will allow me to make changes to the settings in any way. I've logged in from a different account on the same computer and the problem does not occur, so it is specific to my account. I have tried all of Eric's suggestions. Could someone please weigh in with a solution that works? How do I reset Safari completely without access to the preferences menu within the program? Is there some way to delete files via terminal?

It may not help, but try running/posting the Etrecheck report in your normal account. If the log won’t post, try posting it in Pastebin and provide a link in a reply        Pastebin

You are welcome. Holding down the shift key prevent Safari from reloading anything. Sort of a simple reset.