"You feel relatively safe now... But wait... You feel a presence of something powerful!"
Yeah there'd be a chance that once you've cleared the level of all monsters, a boss monster would appear. This'd either be a too powerful monster to be normally generated on that level - such as a cacodemon on level 2 - or specifically named unique fellow. Regardless, once you've beaten your foe, it'd drop something pretty powerful.
Some ideas for unique monsters:
The Butcher: Demon, carries butcher's cleaver (and can use it). Has two levels in Hellrunner and one level in Brute.
Archibald the Undying: Former human, carries blue armor and two advanced pistols. Has three levels in SoaG, two in Dualgunner, and two in TaN. Also has 50% chance of coming back to life immediately after dying.
Hans Grosse: Former captain, has a blue armor and a minigun. One level in SoaB and in Eagle Eye, and three in Ironman.
Bruiser Brothers: Two hell knights, both unarmed and unarmored, but both drop 1-3 random mods. The other has two levels in Eagle Eye and one in Cateye, while the other one has two in Brute and Ironman.
Pain Mother: Pain Elemental, unarmed and unarmored, but drops several random mods and a random advanced weapon. Spawns special kind of lost souls called Hellspawn: They all have three levels in Hellrunner and one in Ironman.
Duke Eresmus: Baron of Hell, has a baron armor, but no weapon. Three levels in both TaN and Hellrunner. Prefers close combat over throwing acid balls.
Spider Mastermind: Always generated in the end of Spider's Lair. Has Jackhammer (and uses it), two levels in SoaB, two in Triggerhappy, three in Hellrunner, and two in Ironman.
If you have other ideas, post them.