Asynchronous does not help you on latency at all - it's not the latency of the clock that matters. It's the data latency. This is already kind of crippling, as it takes hundreds of cycles to get anything from RAM if it's not in your cache.

Only way to improve that is to make programming languages push either data locality or dataflow like designs, which may mean giving up or reimagining OO.

Error rates (yield) are a serious problem, but if your design is uniform enough you can very well get away with just disabling bits. There's also a less obvious problem with on-chip variation (OCV) - some physical properties have a gradient across the chip. At runtime, there's a temperature gradient as well.