Drupal - Separate frontpage per domain?

In my mind, the big advantage of using Panels is so that you can extend/alter sites like this in the future, without needing a lot of rework. In a lot of ways, Panels provides a framework for futureproofing sites.

While I am not sure if I have used Domain CTools,that is the first approach I would take. I essentially use a similar approach using Mobile Tools in combination with Domain Access for providing split desktop/mobile sites that share some, but not all, content and features.

The access rules that Domain CTools provides will show up in the visibility and selection rules inside Panels.

For the node pages, I would enable the default node override page inside Panels, and then make variants for each of my content types. I would then assign access rules to each, based on the domain.

For the home page, I would make a new custom page and set it as the home page. I would then make two variants, and make a selection rule based on the domain for each.

The other thing to think about is how nodes get used in places other than the node view page. For example, if you should double check your views and add access controls as needed. Assuming the approach outline above, you could also use the Domain CTools access rules. Depending on what other uses there are, you may need to investigate whether you need a custom hook_node_access() for your site.