[cjm42]

Yes, it would cause issues with hosting services that use CNAMES in the way they were intended. e.g www.example.com might be CNAMEd to example.bigwebhost.com so that bigwebhost can change the IP addresses used by example.com without having access to example.com's DNS. Your proposed change would make every site hosted by bigwebhost part of the same domain, potentially leaking cookies to each other.

[lazulicurio]

You could do something similar to how FF implemented their new cookie isolation.

Make the key (original domain ^ final CNAME).

Which probably would still have issues, but I think it's worth looking into.