The best set I own from the 2000's is the City Airport. Which is technically a 1994 set, but it was rereleased as a legend in 2004 (when I got it), so I count it as a 2000 set.
The worst set I have, excluding one Galidor set, is the Worker Robot. I got it with most of the other Life on Mars sets at a local thrift shop. It is just way too small, undetailed, and it is ugly.