Any reason not to use 512-bytes clusters for NTFS?

Smaller cluser size means that a file will be distributed between more clusters (obvious). This means potentially more fragmentation and possibly more lookups to find the clusters. It is the usual speed vs size optimisation. As the hard disks are cheap, I would go for larger cluster sizes, but anyway, you will probably not see that much difference ...

NTFS is extent based (like xfs, ext4 and more on the *nix side) so the slowdown you get from non-extent based filesystems (eg fat, ext3) is reduced.

There's still an overhead though, and where it starts to hurt is fragmentation. Windows is HORRIBLE about fragmentation, try running defraggler to see how even sequentially written files (eg from program installation) can end up in 30+ fragments.

I'd generally suggest 4k as a good size, although if a drive is to be used for large media files 64k or larger can help.

http://www.defraggler.com/

One reason to go for a 512 byte sector size is if you are planning to use Microsoft Windows Backup on a server. Amazingly if you use Windows 2008 (I do not know whether this has been fixed in Windows 2012 or later versions) but the backup will fail if you use the default 4k sector size on an off-the-shelf usb external hard drive! I recently purchased a new Seagate drive after speaking with Seagate's tech support to confirm that this was possible and I could reformat the 4k sector size back to 512 bytes and my backup worked. It is strange that neither Seagate's nor Microsoft's support website point this out.

The earlier external drives do not allow you to reformat the drive with a sector size of 512 bytes; the minimum is 4k.