From what I've seen so far, to me it's a tossup between Bearshare and Gnucleus. Bearshare gives you the option to install various pieces of spyware, but it's just an option. Both feature multi-source downloads, and are excellent for finding mp3s.
edonkey is excellent for large video files because it does a better job of automating the multi-sourcing, and because it's been doing multi-sourcing for a longer period of time, there's more large-file video content on the network. However, the client is unstable (forces the occasional reboot on my Win2K system), and the interface is clunky (you have little control over who you download from and who downloads from you).
Right now I'm experimenting with Direct Connect. IMO it's not good for large video files due to the lack of multi-sourcing. You're at the mercy of the other guy if he goes offline, and also at the admins, who can boot you at any time for any reason. The interface is very clunky, and while it's far better than Hotline, it's still annoying.
The major advantage to supporting the gnutella network is the fact that because the protocol is open source (and so are some of the clients), there's no specific target for the RIAA/MPAA to go after.
I haven't tried other filesharing clients yet, so there may be something else out there.