The battle with Klauth, one of the most dangerous enemies in the entire campaign, possibly even stronger than Morag. How strong is he? The game hands you a way to weaken him to "Badly Wounded" by beating a Mini-Boss, and he's still one of the worst bosses in the game. By the time he falls you are going to feel like a hero; if you beat him without gimping him with the offered method to do so, you earned yourself bragging rights.
If you manage to beat Morag in the first game without reaching level twenty, it's already pretty awesome— but when the finishing blow is landed by your halfling henchman while you're running away and pissing yourself in terror, that's a Crowning Moment of Awesome.
Confronting the white dragon Tymofarrar and making him go Oh Crap! when he notices the phylactery you're carrying can be used to easily kill him, and he offers you any reward he can give if you let him live. You can successfully intimidate a dragon into doing whatever you want.
The battle with the Valsharess is intensely atmospheric. After spending the entire game building up the confrontation, it's a Duel Boss with a powerful sorceress, the two of you battling before a flaming pit as the devil she's summoned hovers over it just watching.
For extra cool points, depending on the exact position of her when you deal the final blow, Mephistopheles will break free of his bonds after the fight, leap up, and land on her bleeding corpse before the dais; a final insult to her after he clearly hated being under her control.
The battle with Grimnaw and his allies allows you the potential to see the fight that never was in the original campaign: Aribeth vs Maugrim.
The cutscene that precedes the battle with the Third Guardian in Hordes. He orders his minions to attack you... and the minions hesitate because your character has become such a Badass, even devils are afraid of them.
This is followed by a Zerg Rush of many, many minions, with your and your companions in the middle of the area fending them off. If you're at a high-enough level this can result in a massacre as your character turns in place to strike down enemies in one hit.
The ending of Hordes. Play your cards right and you can become the ruler of Cania with Mephistopheles as your lackey, and you turn the capital city into a magnificent metropolis rivaling Sigil.
As a separate part of the ending, if you're playing a male character, not only can you take both Aribeth and Nathyrra as love interests, but with the proper dialogue paths you can convince them to share you with the blatant implication it's going somewhere sexual. It's Wish Fulfillment for male gamers, but it's at least an awesome example of it.
On a flip of the above, if you're a female character and your True Love is the Sleeping Man, you can awaken him and get him to help you fight the Final Boss. A Celestial duking it out with an Archdevil is an awesome sight to behold.
Beating the Final Boss, Mephistopheles,, the second most powerful Archdevil in the Multiverse. Enraged, he can only beg you to spare his life before you decide his final fate. After all the pain, harm, destruction and deception he caused, it's very satisfying to slay him and send him back to the Nine Hells.