Physical size isn’t really the issue.
My first thought would be the drive speed (5400rpm or 7200rpm) after that I would say your preference, the 2.5” might be lighter in terms of weight so less chance of drop damage as less mass but really not much better.
While not related to performance 2.5" drives have the advantage of being capable of running solely on USB power. So you don't have to use a separate power adaptor. Unlike 3.5" drives which require 12v input.
Thanks for the replies. I believe both drives are 5400 RPM. Maybe more cache on one? Not sure. Mainly looking for reliability and transfer rate performance of one over the other (if one actually is faster via real use).
Not really going to be much difference on performance between those two specific units. They are both modern 5400 RPM hard drives, and they won't win any performance awards, and they both have 3 year warranties. Although the Red drive states the amount of cache it has, I couldn't easily find any detailed info on that aspect for the Passport drive.
If reliability is important, I'd be inclined to go the separate drive + enclosure route. For two reasons. First, the WD Red should be more reliable, as external drives tend to get lower quality drives put in them. Second, if the enclosure fails, you can always pull the drive and plug it into either another enclosure or a suitable PC. Which makes it fairly easy to get data off in the event of failure. This isn't always easy with sealed external drives.
Oh, and always remember the old adage; It's not if a drive fails, but when. Backup, backup and backup. (This is a reference to you should always have at least three copies of important data. The more copies across more drives the better)