We're pretty lucky in WoTLK, since it looks like two long neglected lore questions, when Tirion Fordring was going to try resurrecting the Silver Hand, and what happened to King Varian Wyrnn, are going to be answered. That doesn't mean that many more haven't been left wide open.
For example, What is up with Deathwing? If you've hung around the Dragonmaw camp at Netherwing Ledge long enough, you've probably seen them receive a certain visitor who suggests the lord of the Black Dragonflight isn't quite dead yet. There's also the issue of what Azshara is planning, and whether she is guiding the Naga and Murlocs of Azeroth to some greater, sinister purpose. It would also be nice to know what Malfurion is up to in the Emerald Dream.
Even on a "smaller" note, we have to wonder what Sylvanas wanted with those Bloodstone Relics, or what Magatha is up to. Given that it was bad enough that the Arikara came after her, and evidence points to her people being in league with the scourge-allied Razormane Quillboar and looking for ancient Necromantic knowledge, I have to think she's up to something huge.
We can only hope Blizzard will get back to these lore lines sooner rather than later, but since WoTLK is getting back to some old threads, I'd say the hope is pretty good. What lore thread bought up by a quest or another source do you want to see addressed or finished soon?