When thinking over the final episode of S3, I was noting something odd about the scene when Sam hesitates to kill the child he thinks Lilith is possessing. It led me to realize this is an issue I've been seeing with more frequency, and looking back to S1 I think there really has been a change in the way the show deals with non-recurring characters.
(1) The view of families is becoming increasingly negative in its portrayal on the show.
(2) The characters of the week in general are becoming more disposable this season.
What do I mean by #1? This season it seems no one has family feelings the way the Winchesters do. In both TKAA and in No Rest, we have mothers ready and willing to kill their daughters, and yet it's Sam we see hesitating to do so in the latter. How many mothers do you know would be urging a stranger to kill their child regardless of what that child had done (even their adult children)? I mentioned this problem in the previous episode as well when I talked about Dean burying the exorcised body. I guess we're supposed to assume no one is going to be looking for this person, even though a missing family member is what got the Winchesters back on the road.
Granted the Winchester model of family is perhaps one best not followed by the general public, but I thought that the family models early in the show with Haley in Wendigo, Jake who eventually sacrifices himself for his grandson in Dead in the Water, Rebecca's devotion to her brother in Skin, etc. were all much more closely tied to Sam and Dean, and gave the Winchesters connections to the people they helped. Families, in fact, were a theme in many of the S1 episodes and they were shown quite favorably. Even in the Benders the villains were offset with Kathleen's lingering devotion to her missing brother. The major exception was Max's family who was used as a negative contrast to the Winchesters' more favorable one. Even so, I think the twist of that episode worked because the idea that Max was the source of evil is shattered when it's revealed that his family created his dysfunction. This is seen as aberrant.
By comparison in our admittedly short S3, families (as opposed to couples) do not appear in particularly positive ways. We don't know how many families in TKAA recognized things were terribly wrong with their kids but the ones we did see didn't portray a positive model. Even Lisa quickly turned against the changeling even though you'd think an ordinary parent would think she was hallucinating sooner than she'd imagine her son was not her son. In Bedtime Stories we have a father who was blind to the problems in his own household that led to his daughter's suffering and death. In Red Sky, family betrayal is at the center of the storyline. In Dream, Jeremy's dad has abused him and created the problem he is suffering from and is now willing to kill to alleviate. The family angle in Ghostfacers is there but rather unexamined in the story, and we finally have Bela's ugly family history exposed in Time. In Long Distance Call, it's questionable what sort of family ties Lanie and Simon have now that their mother's dead, but she's hesitant to bother her father at work, and expects she won't be supported if she confides in him. We also see another family torn apart with the cop and his daughter (and, I'd argue, one could infer that her death has ended the marriage).
Interestingly the one family tie that harkens back to S1 occurs in Mystery Spot, when Sam (and the episode) ignores the daughter passing out flyers trying to find her father. In fact it is likely her efforts that brought the Winchesters on the hunt in the first place, as she publicized her father's disappearance. Within that episode Sam's complete obliviousness to her problem and Dean's follow-up harkens back to Wendigo, where Dean persuaded Sam to pay attention to these people who need help and stop focusing just on his own obsession. That message didn't sink in all the way, and in Mystery Spot Sam was pretty much on his own, following his own path. In fact, as it's revealed, had Sam followed up on the original (external) problem, he would have found the answer to the riddle much sooner.
I think the various family connections in S1 weren't a coincidence -- they were there to mirror the Winchesters' own relations and give us a chance to learn about them. So although I find the family connections in this season more haphazard, some such as in Red Sky were fairly clear in their commentary. Perhaps the negative views this season are there to drive home the idea that as important as family is, it can be a very negative thing as well. Certainly that was part of Dean's message to Sam in No Rest.
So while I could see the darker look at families being tied in to the overall Winchester arc, I think a case can be made that outside characters are increasingly disposable to the Winchesters and the show. As late as WIaWSNB Dean gave up a happy dream in part to save the lives of the people he'd once helped. Yet that same season, Sam in Playthings was looking at helping victims as a way to save himself. I think Dean has always been more selfless in this sense, but at the same time he has also enjoyed the hunt for its own sake more than Sam has. And perhaps as their own problems have become central, those around them have become more irrelevant. A quick look back will, I think, point out clear differences.
In every one of the S1 episodes from Wendigo to Route 666, The Benders, Something Wicked, and Provenance, Sam and Dean were seen at the end of the episode saying farewell to, or somehow finding closure with the main characters of the week. Even in Shadow, one could say this happened, because although there was no victim of the week, we saw Sam and Dean saying goodbye to John. In Nightmare we see Sam and Dean seeing that Max's stepmother has her own sort of closure (explaining to the police what has happened), and in Hell House they see Ed and Harry off (if only to enjoy their own jokes). Only in the last three episodes, where they are wrapped up in the family case, do we not see this happening.
We do see some farewells in S3, but I think it's significant that the people they have closing scenes with are mostly hunters or fellow travelers, not ordinary people and victims. So we see Tamara off in M7, and Bela in Red Sky and Time. Indeed some of these final scenes aren't even closure but simply further the plot, such as with Bela in Bad Day, Ruby in Sin City and Malleus, or even one another in Fresh Blood, SPN Christmas, Dream, Mystery Spot, and Long Distance Call. Some other goodbye/closure scenes are largely for Sam and Dean's sake as much as to give us an idea of how the victims are faring. The first is Lisa in TKAA, which gives us an idea of where Dean's head is and confirms finally that Ben is not his son. The second is the doctor in Bedtime Stories, though this is again more of a plot issue as it allows Dean to recast the episode's message to Sam as the negative effects of not letting go. In Ghostfacers we see them saying goodbye, but it is primarily so that they can wipe out the tapes that have been made. The only exception I think would be Jus in Bello. We do get a plot point in that Henriksen tells them he has listed them as dead. However it's a clear farewell, not just to him, who we could list as a type of hunter (not to mention recurring character), but more significantly to Nancy and the deputy. In fact we get a farewell twice, since Sam and Dean find out later that they died. These are people who clearly mattered.
Of course even back in S1 there were people that Sam and Dean saved in passing who were never followed up on, such as the activist in Faith, or the couple in Scarecrow. But somehow these seem less egregious than loose threads such as the little girl in Bedtime Stories, or the father trapped in the bag in SPN Christmas. To some degree I think this is a matter of screen time. In S1 there were almost no recurring characters. So in S2 when we begin to get some, it is these characters who we see closure with rather than victims ("No Exit" is a good example). In another way though, I see it as both an example of the increasing callousness of both boys, and the increasing inward gaze of the characters and the show.