Q: Safari can't open the page (WebKitErrorDomain:300)

Please read this whole message before doing anything.

This procedure is a test, not a solution. Don’t be disappointed when you find that nothing has changed after you complete it.

Step 1

The purpose of this step is to determine whether the problem is localized to your user account.

Enable guest logins* and log in as Guest. Don't use the Safari-only “Guest User” login created by “Find My Mac.”

While logged in as Guest, you won’t have access to any of your documents or settings. Applications will behave as if you were running them for the first time. Don’t be alarmed by this behavior; it’s normal. If you need any passwords or other personal data in order to complete the test, memorize, print, or write them down before you begin.

Test while logged in as Guest. Same problem?

After testing, log out of the guest account and, in your own account, disable it if you wish. Any files you created in the guest account will be deleted automatically when you log out of it.

*Note: If you’ve activated “Find My Mac” or FileVault, then you can’t enable the Guest account. The “Guest User” login created by “Find My Mac” is not the same. Create a new account in which to test, and delete it, including its home folder, after testing.

Step 2

The purpose of this step is to determine whether the problem is caused by third-party system modifications that load automatically at startup or login, by a peripheral device, by a font conflict, or by corruption of the file system or of certain system caches.

Please take this step regardless of the results of Step 1.

Disconnect all wired peripherals except those needed for the test, and remove all aftermarket expansion cards, if applicable. Start up in safe mode and log in to the account with the problem.

Note: If FileVault is enabled in OS X 10.9 or earlier, or if a firmware password is set, or if the startup volume is a software RAID, you can’t do this. Ask for further instructions.

Safe mode is much slower to start up and run than normal, with limited graphics performance, and some things won’t work at all, including sound output and Wi-Fi on certain models. The next normal startup may also be somewhat slow.

The login screen appears even if you usually log in automatically. You must know your login password in order to log in. If you’ve forgotten the password, you will need to reset it before you begin.

Test while in safe mode. Same problem?

After testing, restart as usual (not in safe mode) and verify that you still have the problem. Post the results of Steps 1 and 2.

So - I've been searching for a solution to a similar problem, with no luck so far.  Additional details are below, but let's start with the salient part - the test results:

Test 1:  creating a new user allows me to access the page as normal.

Test 2:  opening in Safe Mode DOES NOT allow me to access the page.  (I was sort of shocked by that.)  After restarting the problem continues.

In my version of the problem, whenever I try to access Humble Bundle (https://www.humblebundle.com/), I get the following error from Safari:

Interestingly, I also get something similar from Chrome:

BUT - it turns out I can open it just fine in the version of Firefox I had installed but not used for quite a while (v38.0, and then updated to 40.0.3 just to see). 

I am perplexed.  I did a bunch of moving out of old stuff in my ~/Library folder (which was probably good anyway) but to no effect.  It must (obviously) be something that Chrome and Safari are sharing, but Firefox is not, so presumably something webkit-related? 

I can obviously work around it, but it's driving me crazy so I'd love to figure out what it is.  Any further suggestions?

So - no real progress on this, but I thought I'd add a suspicion in case anyone else is looking at it.  I've determined that a likely culprit is that Chrome and Safari use the Mac's Keychain for certificate management, whereas I believe Firefox does not.  It's not a smoking gun, but it does seem likely that the issue lies somewhere in there.

I tried doing some of the things in this post:

http://apple.stackexchange.com/questions/53562/safari-cant-connect-to-https

Notably, disabling the security plists (though I didn't reboot, only bounced Chrome), but so far at least no effect.  I may keep messing with it if I have time.

Having the same issue. Chome and Safari suddenly stopped being able to access certain websites.

No problems with Guest user.

No problems with Firefox.

No problem using command line to access URLs that are having issues.

It seems that certain linked files (like a css files) of a website do not download or do not get interpreted correctly. A chain reaction follows such that nothing gets rendered. Using developer tools in Chrome more clearly shows this.

Actions taken:

Remove ~/Library/Caches/com.apple.Safari

Remove ~/Library/Safari

Remove ~/Library/Preferences/com.apple.Safari.*

Unfortunately I have no solution either right now...

Safari - Unsupported third-party add-ons may cause Safari to unexpectedly quit or have performance issues

Safari doesn't load a page or webpage items are missing

Safari/other browsers – Website not loading