Sam and Jessica.
I always had a soft spot for them being together, you could tell that Sam really loved and cared for Jessica. She was good for him, and he was for her.
Also, I honestly feel that Sam/Jessica are the only genuinely real, believable and healthy couple on the show. Everything else the show has done in terms of "romance" seems rather rushed and forced in an unconvincing and sometimes disrespectful manner, whereas with Sam and Jessica they had more warmth and respect and there was definitely a connection, a chemistry between them. Plus, the fact that Jessica is rarely seen in a negative light by fandom is one of the rare upsides. I don't know whether it's because she was only featured in the pilot, with some scattered cameo appearances here and there, which was before the female-character bashing that started happening as the show progressed or the fact that she was Sam's first love that makes her off-limits to that kind of judgment, but I consider it a blessing that she isn't hated or disliked since I really think she was the most honest thing Sam has ever had in his life and, again, they were good together. I do believe had Sam told Jessica she wouldn't leave him or anything, but try to make sense out of things.
In fact, my personal canon scenario is that Jessica didn't die in the pilot and that, after learning the truth about Sam's past, goes on the road with the Winchesters and learns to be a self-sufficient hunter herself. :)
Following closely would be John/Mary because, how can I not? They did wholeheartedly love each other. I just hate how the show is making it seem like John turned into an asshole before Mary's death. That's just not fair. :(
Rest of the 30 Days of Supernatural Challenge.
Icon not in relevant context, I just don't have any romance-based ones for the show unless it's slash-related so I'm substituting from another fandom, lol.