For every torrent I download, I set its destination to my fileserver, which my Mac is connected to via Samba. When download speeds are higher than about 3 megabytes a second, Transmission will lock up (beach ball) for 10-15 seconds, work for about 10-15 seconds and then repeat.
Moving the data files to the local OS X drive completely eliminates this behavior, even at speeds above 5 MB/s. Finder doesn't seem to have any problem writing to the share at speeds even higher than that.
I posted on the Transmission forums that, when saving to the Samba share, I would constantly see "Prefetch failed, Operation not supported" debug messages in the Transmission log; literally hundreds of them every second for every torrent being downloaded. I suspect this has at least something to do with it, but haven't gotten a response on their forums.
Other than "Just save stuff on your local disk then, dummy", is there anything I should try?