I don't know how most people felt about Runewords in Diablo 2 but they drove me absolutely insane. Having to always have a database opened so I could check to see what I was doing always pulled me out of the game and broke what immersion I could manage to get (having a cat always attacking your feet sorta breaks immersion as well).
Runeword may not be the best name for the system but it was Runewords that originally gave me this idea. Having special recipes drop, something like a stone tablet that could be either magical or rare, maybe even unique. It would function something like a one-time only Runeword in a way. Since I have no idea exactly what's coming in D3, I'll just use D2 items as examples.
Come to think of it, this is sorta like crafting...
Say a mob drops a tablet, we'll call it Flametongue Tablet just because. It would be setup like this:
Requires: 2-Handed Sword, one gem, one jewel, Ort + Sol + Ort runes
Grants: +30-50 Fire Damage, +5 Light Radius, +30 Fire Resist
Basically, fulfilling the requirements expends the tablet and transforms the weapon. It would get the granted bonuses, as well as the bonus from the gem and jewel. The runes would be used and not have their powers granted to the weapon.
To me, this would make using Runes much more...friendly? You wouldn't need some massive database to keep track of everything, it would all be random. Like being able to add a new template on top of an old piece of gear. It could work with pretty much any type of gear also. You have a Two Handed Sword already that has 12% life leech and don't want to give it up? Alright, toss that sword into the tablet and add the goodies on to it. Only one tablet to one piece of gear though...of course.
Anyway, just some random idea that popped into my head. Would increase customization, would make a lovely random toy to play with since a tablet could drop with any of the random modifiers of magical/rare gear, and would still let you alter it somewhat with jewel and gem choice. Some could require no gems, multiple ones, charms, who knows? Anything to make a mixing pot of randomness to play with