Best way is probably to go VotA and then Oasis, rinse and repeat. You can check some WPs Jaetch mentioned if there's an elite next to it.
What I personally did (and how I got loads of keys such that I won't need to go to act 2 for a long time in the foreseeable future): I combined "personal achievements" with the act 2 key hunts. I still haven't found the Murlocket, so I'm going Sewers; I still haven't seen The Tomekeeper, so I'm going Realm of Shadows; I ran Desolate Sands endlessly to get all 10 different Ancient Devices for the achievement; and I'm looking for the ship to get all 6 pages. Oh, and in the Oasis I was looking for Rakanishu and Bashiok besides the keywarden. Couple of things to do, though in unpopular regions, it gives some extra motivation.
I do that, and also, I like doing Shadow Halls and Unknown Depths along with Realm of Shadows. Awesome xp. Also doing the Achievements thingy...still need another 20 unique monsters yet along with a few odds-n-ends.
I don't know how optimal this is in terms of xp per hour but I usually do runs like this:
Start on Black Soulstone (Soulstone Chamber) Quest WP to Archives of Zoltan Kulle (5 Stacks NV running Unknown Depths and Storm Halls) WP to Path to Oasis (Clear Dahlgur Oasis) WP to Ancient Path (Clear Desolate Sands) Optional: WP to Road to Alcarnus (backtrack all the way towards Caldeum)
edit: it pasted as a dif color font and I couldn't figure out which color is default Enjoy GoldenRod