Buffy and Xander
I'd heard about Buffy the Vampire Slayer during its first season, and heard a lot more about Buffy and Angel, but I hadn't watched even a second of it and basically knew nothing other than that Sarah Michelle Gellar (Kendall from All My Children) was in it. One day, I caught an episode, but I was only half paying attention so I didn't get the character names. I just knew that by the end, Buffy -- yeah, I knew her -- and the gorgeous, dark-haired dude (obviously this Angel guy) had some serious chemistry and totally got the fuss. A little research and another episode later, I found out that no, the dark-haired dude wasn't Angel, but rather Xander. Then, I met Angel. I wasn't impressed with him, his looks or his chemistry with Buffy. Still, I figured he's a vampire, she's a slayer, maybe Buffy and Xander have a chance and the show is awesome!
Five and a half seasons later, I was still watching it, still mostly loving it even if it was clear I was never going to get my beloved Xander and Buffy, damnit! Then came "Once More with Feeling" and despite SMG and James Marsters' admitted chemistry, I couldn't get past the fact that Buffy -- no matter what her situation -- would never, ever, ever do that if she was still the character I'd followed the last five+ years. So I stopped watching. I tuned in for "Seeing Red" and enjoyed the Buffy/Xander scenes, and I rewatched OMwF a few times -- I still have the soundtrack -- but every time I watch it, time has not diminished my disbelief with Buffy's actions, so not only was Buffy/Xander doomed, so was the show for me. Ah well.
With the comic book going, it's still possibly I may eventually, someday get Buffy/Xander, but it won't be the same. I've accepted that this is my one all-time huge, completely obsessed with ship that will never happen. Ah well. But damn, Nicholas Brendon and Sarah Michelle Gellar sure had some amazing chemistry.
George and Izzie
I still contend that Katherine Heigl and T.R. Knight have wonderful chemistry. I shipped George and Izzie from episode one, and there were certainly moments along the way that showed that potentiality. And then Shonda Rhimes actually *did* put them together, but in such a horrible, terrible way that it pretty much blasted any shot at success they had. A married George, a drunken George and Izzie, Izzie acting self-righteous about their love?! Oh, Lord, no. It was there, the brilliant potential and I absolutely believe Rimes when she says it was planned all along, the choice of execution just fucked it up beyond repair.
On the plus side, thanks to the season five ending, having it end with a possibly dead Izzie see a possibly dead George says to me that if they DO die, they're together forever. And even if only one or neither die, that when they're at the end, it's each other that they see. So, the Georgie/Izzie lover in me to that says ... awwwww!!! Together for eternity. At least there's that to hold on to.
Harry and Hermione
Sigh, there was a period where I was rereading the books and making notes that "proved" that it would be Harry/Hermione obsessively. Seriously. I still have the notebooks to this day. There's a lot of notes. I spent a lot of time on message boards debating it. I was (and still am) a proud Harmonian. Then came book six. Yeah, there went that dream.
I can write pages and pages about this, but the bottom-line for me is that JK Rowling should have let go of her planned epilogue and paid attention to what she had created: An amazing love story, filled with such nuance and refreshing in it's non-combative, delicate power. There was such a depth to Harry and Hermione's relationship, that frankly, I don't see how any other character could come close to touching. They always, *always* choose each other. They are always, *always* there for each other. They love each other completely and absolutely, and see each other completely and absolutely -- all the good and and the bad and the inbetween -- and still love each other completely and absolutely.
What a waste. What a waste. (And, damnit, Luna was *perfect* for Ron! He needed someone who adored him and put him first and foremost once and for all, and Luna did that for Ron!)
House and Cameron
No, the show isn't over yet, but considering the direction of the last season, it's pretty obvious that this ship is pretty much dead. Yes, it still has a chance of resurrection, but I'm not holding my breath. For me, I fell for them season one, right away, because I felt that Hugh Laurie and Jennifer Morrison had wonderful chemistry -- yup, the 'C' word again -- and I loved how their story was being told in between the lines and cracks. How Cameron was growing and changing for the better, and how House was always fascinated by her unending compassion for everyone and everything. I just loved them, and still have a teeny bit of hope. But yeah not much at all.
Wolverine and Rogue (movie-verse)
Hugh Jackman and Anna Paquin have some of the finest chemistry I've ever seen between two actors. Characters who shouldn't be shipped; who should have come across as wholly father/daughter didn't ... because these two had hot, crackling chemistry out the wazoo! I so wish that they'd just ignored the comic-canon -- as they already had with so many things -- and just gone there, damnit!! Man, they are so good together. And I continue to hold out hope that someday, Jackman and Paquin will do another film together. It could happen!