You can't fit two 3.5" drives in a single 5.25" space, so the only choice would be 2.5" notebook drives. I'd say that with two of these and reasonable placement, you don't have to worry about heat and vibration that much. These things are designed to be used in a very unstable and cramped environment.
IMHO a ribbon cable is not a good idea. It is a PITA to route and it obstructs airflow. Your product will be much easier to manage if you use standard round SATA cables.
Ideally, you would design the thing so that one can hot-swap a failed hard drive.