Any drive that's more than 50% full will be dramatically slower than when it was new. It's not just fragmenting; your data will start occupying physical drive regions that are closer to the spindle, where linear speeds are slowest. It just takes more time to read and write data. I keep my data drives until half full, and then re-purpose them as backup drives (where performance doesn't matter ... I'll fill a backup drive all the way).
As far as scratch drives for PS, it's questionable economics to try to speed things up with fast, dedicated drives. This used to be the only way, back when PS was limited to a couple of gigabytes of RAM. Now it's generally better just bump up the ram so you use scratch as little as possible. Especially true if you don't have an earlier mac pro (like mine) that uses ridiculously expensive error-correcting DIMMs.
It's helpful to turn on the "efficiency" info option on the bottom left of the main PS window. This will tell you the degree to which you're using the scratch disk. 100% efficiency means not at all. Once you get to 70%, you'll probably notice the slowdown. There are many things besides file size effect scratch use. Probably the biggest one is the number of history states you ask PS to remember. If you can give up a little history, you'll use less scratch. Also the nature of the operations you do in PS. Anything that effects the whole image is going to require more scratch than something that just effects a single image tile. And of course, anything that effects multiple layers will require more than something that effects just one. Photoshop actually writes the minimum number of tiles to scratch that it can get away with.
If things get sluggish and you've tried everything else, you can purge the history states, and a lot of other cached stuff (edit menu). This gives a fresh start.
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