I actually think Portal would be a better killer VR app than HL or LFD. It would appeal to a much larger base, including more casual game players.

If we're talking mainstream breakthrough.... If EA weren't so backwards, and assuming the hardware were ready, The Sims VR would cause an earthquake.

Also, a next generation incarnation of Minecraft would be a prime candidate. A world you can 'live' in, that is easy to randomize and wouldn't take five years for devs to build first (ala Skyrim).