Judging from a 29-page thread brewing on the Apple support forums over the past few weeks, the iPhone 4S is suffering from a glitch where outbound calls have no audio coming from the earpiece.
Based on the accounts of those postings, the problem seems to revolve around some sort driver issue between the iOS software and the iPhone 4S hardware. People have no issue with incoming calls or other aspects of iOS that use the earpiece, such as Siri. Originally, people thought the problem was due to connection confusion with Bluetooth headsets, but then it was revealed that those who had never even used the Bluetooth connection also encountered the same fate.
Users say that the problem remedies itself when speakerphone is toggled on and off, Siri is activated, or headphones are plugged in, then unplugged. But obviously, these are just workarounds for a problem, not a fix.
Furthermore, MacRumors posted this week about more call problems: one issue involves echoes and poor audio quality when using a bluetooth headset, and the other involves a persistent static sound during conversations.