I have about 300 as well, though not are all turned on. I used fontbook for about 2 months with panther (testing) and had no issues, no slow downs and no stability issues either.
I also had my fonts in 5 sets, 1-2 sets turned off and some fonts in each remaining set turned off. So I didn't have 300 fonts turned on, but then that's why I use font management apps. I use Suitcase normally but wanted to try out fontbook. A few tweaks and instant activation and fontbook would be more then enough for those normal designer. (Not the ones around here who claim fontbook sucks and I guess they are using all of their 1,000+ fonts all on that one single 8x10 flyer)
If you know how to turn on and off, you shouldn't have much problems.