I had actually attempted to get into Supernatural some years ago, when my college roommate presented me with the full first season, and as I once again started the series I was quickly reminded of why I bailed the first time. But many friends had assured me that once you get passed season one or so it starts to "get good". I was not disappointed.
Season 1 &2
Season 1 is kind of a grim initiation. Were it not for certain important plot points and vague character development I would simply recommend skipping it. But I think there is something to be learned from the first season, and it does give a basis for the rest of the series. Sadly I cannot quite recall the episode at which the series started to improve, but I remember being significantly more captivated by mid-season 2.
In the first season I found the acting to be, at times, quite poor. Some of this can be attributed to the writing, where the story or dialogue comes off as awkward or stilted or just plain bad, but there were certain moments when characters - such as Meg's first episode or even at time Sam and Dean - were difficult to watch. And the writing itself was sometimes dull and unimaginative. I didn't care much for Sam or Dean during the first season. Their character's were flat, predictable, and completely cliched.
Female characters are arguably non-existent in Season 1. Sure there are plenty of pretty victims to scream and cry and otherwise be the damsel in distress for Sam and Dean as they travel across the nation on their lonely, manly quest, but rarely/never do these women have any sort of long term relevance, and most we never hear them mentioned of again. It's really quite sad to see.
Personally, I recommend throwing on the first season while you're doing the dishes or painting a landscape or crocheting a afghan and just letting your attention split between the two. By season 3 this wont be necessary.
Everything Else (Season 3 and On)
Season 3 starts off with a distinctly different mood and anyone who is looking for it will notice the change. More solid drama begins in this season (and only gets steadily thicker as the series progresses) but it is shaken up with moments of genuine humor and light-hearted...ness.
The series does become quite angsty at this point, and at times the situation involving a season's overarching plot line is all but hopeless. Sam and Dean are forced to face certain hardships, and on occasion it is hard to know (or easy to forget) why exactly they are fighting so hard against an all but impossible situation (even if the easy solution is unpalatable). If not for the comic relief - which is thankfully abundant in Dean's sarcastic quips or Castiel's charming ignorance - this could be a fairly difficult show to get through. But rest assured, the humor increases noticeably at Season 3, without undermining the gravity of the show. There were multiple occasions where I found myself laughing out loud at some of the dialogue or situations, something that was lacking in Season 1.
Beginning about halfway through Season 2 and continuing on throughout the rest of the series, we see - in my opinion - a dramatic improvement of the show as a whole. Sam and Dean's acting gets noticeably better, as does the overall writing of plot lines and dialogue. Starting in Season 3 we also see a significant increase in relevant female characters, who exist to be more than just a pretty face for Dean - or occasionally Sam - to lust after. Sadly, this doesn't last and the show is still outrageously male-dominated.
There is nothing perfect about this show (except perhaps the smoothness of Misha's unnaturally beautiful face) but it is none the less worth the effort. The plot is engaging (once it really starts up) and you could lose many an hour on this show. If you find the plot intriguing at all, or if you share interest with fans of Supernatural I definitely recommend giving it a shot. And don't judge it until you are well into Season 3.