In Knocked Up, Seth Rogen is a goofy but loveable stoner who gets his one-night stand Alison pregnant. In 50/50, Seth Rogen is a goofy but loveable stoner whose best friend Adam gets cancer. His relationships with the two characters and their unexpected medical dilemmas unfold in a bizarrely similar fashion, because Seth Rogen has a very small yet specific range (involving beards and throaty chuckling).
Seth Rogen starts off trying to do the right thing (or at the very least, trying not to do the wrong thing). He happily takes time out from his busy schedule of smoking weed and doing absolutely nothing else and takes Alison/Adam shopping for self-help books so they can better cope with the baby/tumor growing inside them. This shows his compassion, because when your friends are going through troublingly uncertain times, the best thing to do is buy them books, rather than actually try to comfort them yourself.
However, before long ...
In both films, it only takes a few weeks before Seth Rogen starts thinking of ways his friends' respective conditions can be manipulated to quench his relentless thirst for vaginas.
In Knocked Up, Seth tells Alison that the upside to her pregnancy is that "At least we don't have to use a condom," because having more unprotected sex with Seth Rogen is enough to put any woman's mind at ease.
"It'll be just like regular sex with me, except you already know I've gotten you pregnant, so you can cry the whole time."
In 50/50, Seth takes the newly bald and painfully suffering from cancer Adam out to pick up girls, using Adam's condition to prey on their sympathy. Impossibly, this results in Seth getting laid (and Adam having brief and awkward sex that he has to abruptly abandon because his cancer is hurting him too much).
But the pity-sex roller coaster can't continue forever, and ultimately ...
The pressure of having a baby and coping with cancer build up to breaking points in Alison and Adam, respectively. Both of their inevitable shit-losing eruptions occur in a car, with Seth Rogen trapped firmly in the blast radius.
Alison flips out on Seth as she's driving, because he's broke and generally useless, and dumps him out on a random street corner in Los Angeles.
He looks like he's trying hard to remember what a job is.
In 50/50, Adam insists that Seth let him drive his jeep the night before his likely fatal cancer-removal surgery. As soon as he's behind the wheel, Adam has a nervous breakdown and throws Seth out of the car, admonishing him for taking his cancer on a trawling pussy hunt.
It isn't actually cold outside. That's how it always looks when Seth Rogen exhales.
Seth seems like the world's biggest dick helmet, until ...
In Knocked Up, Seth absolves himself of several months of shiftless marijuana addiction by reading What to Expect When You're Expecting and tossing Alison a few choice pregnancy facts while she goes through contractions in the bathtub.
"I didn't even think you could read!"
In 50/50, Adam finds a copy of Facing Cancer Together full of penciled-in notes next to Seth Rogen's toilet, letting Adam know that Seth cared all along.
"Why else would he write in this book while taking a shit and then completely ignore all the advice it gives?"
In both movies, the big twist revealing Seth Rogen to be a good guy instead of the callous buttlord he demonstrated himself to be is the fact that he bought the self-help books he took his friends shopping for in the beginning (even though he went out of his way to ridicule said books the entire time). Truly, Seth Rogen is a champion of selflessness by which all others should be measured.