A long fight against the Core. While building up for a major attack, I noticed several key areas of my production and defenses going up in massive explosions, and it took far too long to realize they had nuclear weapons. Fortunately, enough survived to build back up. One crippled Guardian turret(decent-ranged artillery gun) managed to hold the forward line long enough to get some anti-nuke defenses built, then get reinforced by more turrets.
A major airstrike aimed at crippling the Core was a dysmal failure since I greatly underestimated the power of flak weapons(which are the only ground weapon that can hit strategic bombers). After getting another air force ready, I decided to launch a nuke of my own ahead to create an opening for the bombers.
And the nuke hit their command center. I win.
NOTA, a Total Annihilation clone for Spring.
Different game, but managed to clear a place filled with orcs that look very suspiciously like Warcraft orcs, and women with katanas and very powerful bows, the latter enemy was serious threat close range. I brought in an NPC spellcaster for support, who turned out to be almost completely useless for anything but being a mule(and even then, she had a tendancy to disappear at times). The boss of the place managed to two- and three-shot me several times, until I figured out a tactic of telling my support mage to stop summond and start hitting things with a bound axe, and then kissed the boss, paralyzing her but tiring me, then using a power to steal most of that fatigue back. Then me and my partner just slashed the boss to death.
Loot was extensive, partly due to NPCs being completely unaffected by encumberence(meaning Burden spells are 100% worthless). So now there's a dungeon full of dead orcs and dead naked girls, many of whom are either decapitated, or had an arrow that caused such extensive blood loss they were still gouting it several hours(or days? I don't really know how much game time I spent down there) later, and I managed to make about 30k from the whole thing, plus new, awesome weapons.
TES: Oblivion, with Hentaimania, CM Partners, and Deadly Reflex, among other mods.