From Wikipedia: [FriendFeed] had on average one million monthly visitors ... [and] was bought for $15 million in cash, and $32.5 million in Facebook stock.
I figure after the first million users, your embarrassingly parellel app server layer is not your bottleneck, it's getting the database to scale.
Personally I would go with async DB, or have DB access in its own thread(s) and async communicate with that.