One,the whole Tony B. storyline. Tony let his favoritism affect his business relationships with both Johnny Sack and Phil,insulting and enraging both of them,putting the entire Family at risk,and leading to the loss of Bobby and(probably) Sil.
Tony's other big mistake was more of an ongoing thing,than a specific incident,and that was his inability to keep his temper in check. Killing Ralphie,beating up Phil,and the sadistic assault on Coco were not the acts of an in-control Mafia Boss.
I know that Coco insulted Meadow,but Tony should have asked for a sitdown first,especially given the shaky truce between the two Families.Additionally,remember that Coco only said some inappropriate things,he didn't assault or physically harm Meadow.