In Google Image Search (the web interface) you can restrict your search results by a single domain. It appears that the same rule applies to the API (http://code.google.com/apis/imagesearch/v1/reference.html#_methods) but as far as I know, the “one site” rule isn’t documented anywhere (other than never mentioning multiple sites).
Does anyone know if it is possible to restrict a search across two or more domain names via the web interface OR the Image Search API?
This is not supported. The Google Image Search API is also being deprecated, so it would be best to search for alternatives anyway.