Sam and hubris
deadendtracks made some brilliant posts about Sam in season 4 and 5, with special focus on Swan Song (here and here).
This highlighted for me that - for me - Sam’s biggest flaw, the one with the most dire consequences, is his hubris.
It made him fall for Ruby’s ploy to go after Lilith, convinced he was the only one who could do it, and convinced his way was the only way to go, thereby releasing Lucifer, it made him say yes to Lucifer (and I can’t recommend highly enough that you read deadendtrack’s posts!), which, if not for Dean showing up unexpectedly in Stull, would have gone wrong spectacularly, and it made him use the spell from the Book of the Damned to get rid of the Mark.
Ultimately, Sam’s ploughing on with the spell, disregarding all other possibilities, including Dean’s own plan, led to the release of the Darkness and the damaging of the Cage, which made it possible for Lucifer to yet again employ Sam’s hubris - pretending he was God sending Sam messages. Which led to Sam going back to Hell - against Dean’s very outspoken concerns - thereby making it possible for Lucifer to make use of the chaos and escape.
Oh, Sam.
(To be fair, I tend to blame it not on Sam himself so much, but on the demon blood he was fed as a baby, which I reckon changed him on a “subatomical” level, and on the fact that he was - from way before he was born - designed to be the vessel for Satan. What I miss from Show is that all of this is actually acknowledged, rather than constantly trying to show us how sweet, brave and sensitive Sam is. He is Satan’s. Vessel. That HAS to have an influence on him.
*steps down from soap box*)