Depends on your drive type tho, in the long term you'll extend harddisk lifetime via reduced disk seek at cost disk stress during defragmentation.
I just wanted to make 100% clear that I didn't recommend the defragmentation of the whole disk. Just defragment the Bitcoin directory only! You can even save defragmenting the "Bitcoin/database" subdirectory because BerkeleyDB is smart enough to preallocate its log files in 10MB chunks.
The other cheap way of reducing fragmentation is running with "-printtoconsole". Then the debug.log will scroll off your screen instead of mutually fragmenting itself with blkNNNN.dat.