I love the idea, but don't quite agree with how you roughed it out. I think that in JRPGs and Zelda games, the McGuffin isn't so much a weapon as a key, allowing you passage.
However, they don't tend to be particularly interesting in their role as a key. It's their secondary uses that make them memorable. Often (in Zelda games in particular), items grant a new form of movement/exploration. For example, in Zelda 3, the following items are all necessary for progression; hookshot, bombs, fire rod, Ether Medallion, Quake Medallion, lantern, hammer, flute, shovel, book, mirror, Cane of Somaria, Master Sword, mirror shield, pegasus boots, two gloves, flippers, and the moon pearl. Of those 19 items, all but 3 (the moon pearl, the flippers, and the book) are useful for more than the obstacles they allow you to pass.
These types of items have to be carefully scripted of course. What I'd do, is add qualities to already useful items to make them quest items. For example:
The Chime of Opening unseals the portal, but also has a random once-per-dungeon buff.
The guards won't let you pass until you get the amulet, which is a regularly generated magic amulet with the GUARD_PASS property added.
The ghost is only vulnerable to the weapon that killed them in life; a regularly generated weapon with the MURDER_WEAPON property added.
Also, OmNomNom's "find the best" idea is very good, assuming your generator is set up to handle it. If not, you might just generate an item with little randomness (the class of weapon the PC is most proficient in, deals damage the enemy is weak against, of an appropriate strength for the difficulty).