Supernatural is a nice little show--what holds it back is its unevenness. My two favorite seasons are 1 and 4. Both were consistently good. Season one was fun and was the best season doing mostly standalones and the occasional big myth episode here and there. I thought the standalones after season one were never as good resulting in very stale plots leaving only the characters to buoy them but in the later seasons the character stuff becomes stale itself. I also loved the simplicity and newness of everything in season one when they hunted monsters of the week before things take an epic turn.
Season 4 was the closest the show ever got to being well-plotted and doing a better job in effectively incorporating the myth arc in a more central manner each week than any other season so the episodes didn't feel like filler. All the other seasons just had the mytharc floating in the background--a lot of times the episodes felt that they existed to spit out a crumb of the plot to seed for further use down the line unlike in season one where the episode itself was worthwhile making a lot of episodes in that stretch feel like a mixed bag. S2, 3, 5 were all over the map giving me whiplash from the wide swings in quality from week to week. S6--the current one--is consistent but consistently mediocre--it is vying with season 3 as my least favorite. It really needed to end after season 5.
As the series goes on its budget is cut back and it shows and the show which was a solid drama in its early seasons starts toying with comedies, parodies and meta commentary that for me undermined the dramatic gravitas it had earned. I still prefer The X-Files or Friday the 13th The Series more but I'll admit it was one of the better sff shows to come out of the last decade.