The only downsides that I know of is that NTFS reserves more space for infrastructure -- like the Master File Table (MFT). By default, formatting a partition as NTFS will reserve 12.5% (or thereabouts) for the MFT. The other downside is that NTFS's CPU/disk overhead becomes pretty high (compared to FAT32) on smaller volumes (like, 100MB or smaller).

The reliability of NTFS and the security options available make it the only real choice, IMO, from Win2000 and later.