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?
It's really a "monster of the week" show - it's not designed for watching like a whole season in 1 sitting.
Later seasons start to have arcs that span more than 1 episode, I'd try jumping to season 5 or something. If you need a plot that doesn't completely disappear after the episode my recollection is it got somewhat better about halfway through it's run.
P.S. Like a season after castiel shows up it was far more watchable, in my opinion. It never turns a Firefly or Trek level of interest or anything, but I enjoyed the later episodes when they were on tv, whereas the early ones with just the 2 guys were trying trying a bit to hard and failing to be interesting in my opinion.