Yes, you can use custom php.ini in virtual domains. I’ve found that it’s
possible also to use registry, but we have not yet checked it.

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How the registry to do per-directory settings.

HKEY_LOCAL_MACHINE\SOFTWARE\PHP\Per Directory Values

Create keys for each directory, then add the entries. So if you’re
website is at c:\inetpub\vhosts\DOMAIN, under the above key, add:

HKEY_LOCAL_MACHINE\SOFTWARE\PHP\Per Directory
Values\c\inetpub\vhosts\DOMAIN\

where \c\inetpub should be replaced with directory where virtual hosts
have been installed, DOMAIN is the domain name where custom PHP settings
are required.

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This works. I used it to turn off safe mode for a given domain.
in HKEY_LOCAL_MACHINE\SOFTWARE\PHP\Per Directory Values\c\inetpub\vhosts\somedomain.org I added the string value safe_mode and set the value to 0. Safe mode is now off locally for that domain while still on globally, just as it would appear when changing values in httpd.conf on an Apache server.