there have been a few species in it that were great that probably couldn't be considered enemies...cant remember the name of the episode but it was the next generation...they came across a planet when everything had been wiped out except 1 house and garden...when the enterprise begin to investigate they keep getting attacked by a ship that appears out of nowhere...turns out the being on the planet was some kind of uber omnipotent god type species who had tried to give up his powers when he married a woman on the planet...the planet had started to get attacked by the same ships attacking the enterprise (although at some point in the past) and the beings wife was killed trying to fight...he then recreated her and their home on the destroyed planet and eliminated the entire species that attacked his planet with a single thought...billions of them in a thought...
as for other proper bad guys...the borg and species 8472...