My most epic drop was Benediction http://www.wowhead.com/?item=18608 back in the MC times. It was a really hard quest finish with an awesome healer Stave reward. It was an really epic feeling.
This post was from a user who has deleted their account.
http://www.wowhead.com/?item=10847 was the phattest loot that ever dropped for me but got ninja'd by a priest.
I would have to say that the first time I ran heroic utgarde keep and get the epic cross bow as pretty sick. It was my first upgrade in WOTLK and the funny thing is the whole time i thought it dropped in pinnicle not in the keep LOL
It had to be my Nemesis skullcap, that damn thing took so many onyxia runs to get. I had several other pieces already and recently gotten the nemesis robes that week too. it remember every warlock in my guild had one and a backup. I remember doing consecutive runs for 4-5 weeks of ony and no luck then when i take a week off while i was gone it would drop and be disenchanted. jesus it was about damn time that helm dropped for me.
There I was just able to run Karazhan and had finally gotten past the "Rogue's arent good for Kara" Stereotype on my server and we start downing bosses. Nothing for Rogue was dropping and I was beginning to give up hope.Suddenly we are at chess and We open the chest and once again no rogue gear. Looking at the drops it was the King's Defender none of the tanks needed it and it had better DPS than what I was using at the time so I took it and put a 20 agility enchant on it.After that my raiding guild refered to me as the King's Defender even after it was replaced lol.
For me, the most epic loot (though not really an epic) sure was Sonic Spear from Murmur. Before raiding Karazhan, I've been there several dozen times on my hunter to get that spear, but it would never drop. Much later, I was helping out some gildies of mine for the Trial of the Naaru: Strength quest, when Murmur finally dropped it. Of course, it wasn't of much use anymore to me, but it sure has a safe place in my bank now...