In a rare moment in The Search, after Sokka expresses his care for Katara, Zuko follows his example and puts his blanket over Azula. Pretty heartwarming to be that gentle to the girl who manipulated and tried to kill him a dozen times... but at the end of the day, she’s still his sister. Both Zuko and Azula have this for their younger half-sister, Kiyi, in the comics.
In Rebound, Mai takes down a room of Ozai loyalists to save her little brother from being indoctrinated into their father's radical group.
In Invincible, the protagonist Mark has a strong big brother instinct towards his younger stepbrother Oliver. Such as when Conquest invaded and Oliver tried to help out, causing Mark to literally throw him out of harm’s way and when Conquest tried to rip Oliver in half, Mark quickly got a Heroic Second Wind. Later when Thragg the strongest Viltrimite nearly killed Oliver by breaking off his jaw and arm, Mark went apeshit, and attacked Thragg relentlessly even managing to draw blood from him.
In Mega Robo Bros, whenever Freddy is threatened, Alez will immediately rush to his defense.
In the first arc (Issues 1-4), Rarity and Applejack (normally Vitriolic Best Buds) are willing to go off by themselves to rescue their respective little sisters, when it seems that Twilight's overthinking will slow everything down.
Also, Rainbow Dash is fiercely protective of Scootaloo, even though (continuity-wise) the arc is set before their official bonding episode.
Celestia shows this towards Luna on a few occasions. It may be a small thing, like shielding her temporarily defeated little sister in the second arc (Issues 5-8) –- or a full-on-powersuicidal attack on her mirror-world Evil Counterpart, who hurt both versions of Luna (due to unexpected synchronization between the two worlds), in the seventh arc (Issues 17-20). She's only stopped by a magical barrier conjured up by Mirror!King Sombra.
The Outside Circle: Pete cares deeply about his little brother, Joey. He basically threatens to KILL anyone who touches him.
In a Star Wars Tales series, "Nomad", mercenary Darca Nyl comes across a mentally handicapped GIANT of a man and his petite sister fleeing from pursuers. One night, while camping, the girl is set upon by a huge and vicious predator. Darca knows that he can't reach them in time to save her, when the man leaps at the beast with a large rock in his hands. Several minutes later, the creature has long since stopped moving and he keeps smashing at it with the rock.
In Switch (2015), Mary, the protagonist, explains that she once saw a boy getting bullied but left pretending she hadn't seen anything. In contrast, when a giant monsters throws a van against her little brother, she rushes to get him out of the way and gets crushed instead (though the Witchblade heals her injuries).
and when Conquest tried to rip Oliver in half, Mark quickly got a Heroic Second Wind. Later when Thragg the strongest Viltrimite nearly killed Oliver by breaking off his jaw and arm, Mark went apeshit, and attacked Thragg relentlessly even managing to draw blood from him.