Since eDonkey uses multi-sourced downloads, it's pretty efficient at getting large files. However, it's a bit buggy (tends to slow down and hang at the end of a large transfer). In general, however, I like it. I would run an edonkey server, but it doesn't work that well, if at all, through NAT.
I played around a bit with Direct Connect, and so far consider it a slightly improved version of Hotline. I'll have to do more testing to have a more definitive opinion, however.