Although HTTPS API request traffic is encrypted, AWS states best practice for cross-region communication is to use a VPN. A VPN will protect the details of the endpoints communicating with each other over the public Internet, and will display less information to an attacker in the network packets. Additionally if you force all traffic between two endpoints over a VPN, if some of the communications are unencrypted by a developer or an application that doesn't properly secure traffic, the VPN will provide an encrypted tunnel for the two endpoints of an application to communicate over the Internet even when SSL is incorrectly implemented, vulnerable to attack or non-existent.
An SSL VPN will encrypt the data as it flows between regions, however it will operate at layer 7 of the OSI model, exposing more details within the packet. An IPSEC VPN, such as that provided by a WatchGuard Hardware Firebox or WatchGuard Firebox Cloud will operate at layer 3 and provide greater protection by exposing less data. It encrypts the data at a point in the packet which hides some of the details exposed by the time the packet is at layer 7.
When relying on a VPN, it is very important to secure the hosts providing the VPN. In other words if you have a hardware device on one side and a software VPN endpoint in AWS, those two endpoints need to be secure because they are encrypting all your traffic. Anyone who can compromise those two hosts could get into your network traffic.
In the case of SSL, every host that is connecting to one another must be properly configured and protected. For instance if you have many APIs for different applications in AWS and you are communicating to those applications from hosts in your data center via HTTPS REST APIs, you must make sure every single one of those applications has SSL properly encrypted to prevent data leaks. One single misconfiguration could be a hole into your network that would allow attackers to scan your internal network looking for more holes, as I will be discussing in an presentation at AWS Community Data in San Francisco on Thursday.
With a VPN the traffic is encrypted at the two VPN endpoints, such as a hardware and software device to and from AWS or two software devices between two AWS regions. SSL encrypts the data between the two SSL endpoints which could be VPN endpoints or two HTTPS REST API endpoints. The implication here is that if you only use a VPN, when the traffic leaves your VPN tunnel and goes further into your network it is unencrypted. For this reason, it's probably a good idea to use both SSL and an IPSEC VPN tunnel for cross region communications and other places where traffic is exposed to the Internet if possible.