I like Defraggler, as it:
- is free.
- is available as a 64-bit version.
- allows you to exclude specific files and folders, and
- has scheduling built-in.
Downsides? None that I can see of. Perhaps it could detect that the Windows Disk Defragmenter is running in the background, and warn you that running two disk defragmenters at the same time is going to slow things down.
You can download Defraggler here.