I'd never use NTFS compression since in a previous version of Sonar it wouldn't even recognize compressed data files...presets and the like. I decided that using Windows compression was a bad idea then.
I already mentioned with the prices and availability of storage these makes the space savings moot.
There is a tangible performance improvement with using the larger cluster size, timed and tested at this end. My data drives contain 1000's of small files, midi, patches alongside many large files also and like I said it works out at around 8 Gb of 'lost' space on a single Tb drive on that average, given that I normally would keep at least 10% breathing space anyway it isn't an issue. If space is
that short another Terabyte or so is just £45
The reduced seek times, sustained transfer rate, less need for defrags, and quicker when you do need a defrag makes things sing a lot nicer in the context of a DAW, and anyone here asking if a 64k cluster size for a new format for a data drive and stating how it is to be used as in the OP my answer would be the same as Jim's, a simple 'Yes'.
My 2 OS's dual boot from a single 500Gb drive which is formatted at the default cluster size, everything else gets the 64k treatment. As far as imaging goes I don't know of a current imaging app. that isn't 64k cluster able. One thing I found with imaging as a single use instance I'm getting a 20% improvement in the time it takes. I'd say that was more than a few milliseconds. It's two whole minutes on a previously 10 minute job albeit on a task that particularly seems to favour the larger cluster size.
I've tried it, tested it, use it and am happy with it and therefore recommend it. As I already said I also wouldn't fret about it if I had a drive already formatted at the 'default' setting that was currently occupied with stuff. On a new data drive however I'd format at 64k everytime.