way to switch up the HDDs while keeping the foam mounting scheme
Is foam on the under-side of the HDD attractive for a reason I don't know of..? I thought that soft-mounting the HDDs with thick rubber bands (O-rings) would be fine. Suspended in O-rings the HDD could have airflow from all sides, which I would think attractive.
Here is one idea: 2 bolts (not wood screws, bolts through the MDF plate) on all 4 sides of the HDD, in a appropriate distance from the HDD. 2 O-rings horizontally and 2 vertically to hold the HDD in place, suspended from the bolts, a little bit away from the base plate.
Another idea: Wood frame, about 2 x 2 or 3 x 3 cm wood (or metal, if that's easier). Build it so that it follows the sides of the HDD with about 1 - 2 cm gap to the HDD. Use O-rings to suspend the HDD inside the frame. Screw 2 - 3 regular hooks into the base plate, and hang the wood frame from the hooks (using "eye screws" or hang the frame directly).
Do you see drawbacks to the above ideas? If you're worried about soft suspension of the HDDs increasing drive wear, then you could add mass to the drives (attach something heavy to the sides of the drives, or hard-mount drives together and then soft-mount the drive assembly). As I see it, lots of people on this forum soft-mount HDDs, and I haven't noticed any threads about abnormal drive failure rates.
A little update to my previous post: If you build a vertical case and you decide to use a fan, then I still think your idea about placing the fan in the center of the case is worth pursuing. That way the MDF plate can silence the fan as much as possible -- if you put the fan at the top or at the bottom as I originally wrote it will be noisier.
If you want to go really crazy, you could build an acoustic trap at each end, and line the inside of the case with absorbent (fx encapsulated gypsum board).