It happens on any domain with php of even mild complexity. Once the 501 errors happen on one domain, it affects almost all the domains on the server.
I just sampled the error logs of one of the domains.
On the same domain, viewing the same page, the error is always the same. All includes fail (generating warnings) and the script stops executing at the first require.
Here's a different domain's log:
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Warning: main(extensions/modules.php) [<a href='function.main'>function.main</a>]: failed to open stream: No such file or directory in /var/www/vhosts/2142tactics.com/httpdocs/webonizer_core/webonizer.php on line 0
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Warning: main() [<a href='function.include'>function.include</a>]: Failed opening 'extensions/modules.php' for inclusion (include_path='.:/usr/share/pear:/usr/share/php') in /var/www/vhosts/2142tactics.com/httpdocs/webonizer_core/webonizer.php on line 0
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Warning: main(extensions/myGroups.php) [<a href='function.main'>function.main</a>]: failed to open stream: No such file or directory in /var/www/vhosts/2142tactics.com/httpdocs/webonizer_core/webonizer.php on line 0
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Warning: main() [<a href='function.include'>function.include</a>]: Failed opening 'extensions/myGroups.php' for inclusion (include_path='.:/usr/share/pear:/usr/share/php') in /var/www/vhosts/2142tactics.com/httpdocs/webonizer_core/webonizer.php on line 0
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Notice: Undefined index: smo_uid in /var/www/vhosts/2142tactics.com/httpdocs/index.php on line 16
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Notice: Undefined index: smo_permit in /var/www/vhosts/2142tactics.com/httpdocs/index.php on line 16
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Notice: Undefined index: smo_permit in /var/www/vhosts/2142tactics.com/httpdocs/index.php on line 19
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Notice: Undefined index: smo_uid in /var/www/vhosts/2142tactics.com/httpdocs/index.php on line 19
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Warning: include_once(googleFuncs.php) [<a href='function.include-once'>function.include-once</a>]: failed to open stream: No such file or directory in /var/www/vhosts/2142tactics.com/httpdocs/webonizer_core/templates/template.inc on line 32
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Warning: include_once() [<a href='function.include'>function.include</a>]: Failed opening 'googleFuncs.php' for inclusion (include_path='.:/usr/share/pear:/usr/share/php') in /var/www/vhosts/2142tactics.com/httpdocs/webonizer_core/templates/template.inc on line 32
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Warning: require_once(linkcol.php) [<a href='function.require-once'>function.require-once</a>]: failed to open stream: No such file or directory in /var/www/vhosts/2142tactics.com/httpdocs/webonizer_core/templates/template.inc on line 57
[Fri Jan 04 14:41:35 2008] [error] [client 65.60.231.37] PHP Fatal error: require_once() [<a href='function.require'>function.require</a>]: Failed opening required 'linkcol.php' (include_path='.:/usr/share/pear:/usr/share/php') in /var/www/vhosts/2142tactics.com/httpdocs/webonizer_core/templates/template.inc on line 57
The notices are caused because the include failed, so those variables have not been set.
This effects both ioncube encoded and normal non-encoded sites.
Thanks for your help, Scott.