I recently acquired Supernatural based on a few positive mentions here on KIA2. I quite like it, but it's a bit... off. These sorts of shows are really about the banter and camaraderie, with the monster stuff being almost incidental. Somehow the chemistry/banter is not quite working for me.
Should I persevere?
Seconded. The series doesn't coalesce until the latter part of season one. That's not to say the rest of the first season isn't enjoyable. It has some hits and misses. However, once you hit the introduction of Scorpius the show is a rollercoaster ride until the end of the series.
My girlfriend and I are watching it now. We're still in the first season. This is her first time watching it since she wasn't alive yet when it air. I haven't seen it since it aired.
That also describes Star Trek TNG, to be fair. A lot of shows are pretty mediocre in the beginning. Even legendary ones.
You get lots of details on second watching.