Sam wanting to be a girl wasn't a problem, they'd just have to hide it from John.
Dean hated that. He wanted to see Sam in the dresses he stole for her. Either from a random lay or a store from a town they won't see for years.
It was innocent at first. Dean being so supportive, brushing her hair and calling her 'little sister' when they were alone, teaching her manners that chicks follow (he only knows them because of how many times he's heard a mom say something about their daughter.)
Dean would never say such things about Sam. Calling her a slut, a cow, a disappointment? It wasn't right, at least not to him.
When Sam finally started getting older, Dean even introduced her to different clothes. Lingerie, bras (he even had the 'it's okay to have itty bitty titties!' talk) and panties.
That's when Dean couldn't look at Sam anymore. Not when she was growing her hair out, wearing lingerie around the motel when John was gone for that small bliss of euphoria. Not when she wore black panties that always seemed to peek over her jeans.
Sam was upset. Why was Dean suddenly distant? Did he hate her? Did he not accept her anymore? She couldn't figure it out until she turned around and caught him glancing at her ass. Of course, he was horrible at being subtle. When she brought it up, he simply said 'a chick is a chick, Sammy.'
That brought up Sam's own question. Was this wrong? Was it wrong to enjoy her big brother staring at her like she was the only girl on the planet?
She had to test it. She began to buy more lingerie, purposefully changing in the middle of the motel room, where she caught Dean's glances from the reflection in the tv. She even started to bend down in front of him, dropping random stuff just to hear his rough voice say her name.
It wasn't long till Dean caught on, till he was sure that she was doing this on purpose. He would give in, but only little moves at a time.
He would grab her waist, let his hands linger on her shoulder, he even 'jokingly' grabbed a handful of her tits. It wasn't that hard, Sam was flat as a board, but he saw the way she was turning red.
They gave up being normal when Dean came back into her life, when she ran away for college.
It was hard, Sam losing her girlfriend — but it was also hard because Sam couldn't help but want Dean to touch her and comfort her in ways that definitely aren't considered acceptable.
After a month, Sam made the first move. She crawled into Dean's bed, sitting on his waist and slowly her hands over his covered chest. The thin shirt was bothering her, she leaned close to kiss his nose, whispering a small 'I love you' before laying down on him completely.
It took no less than a second for Dean's arms to snake around her, holding her close. He wouldn't say it back, not now, not when his mind is screaming about how this was all they needed.