The differences from the donor perspective are relatively minimal. However, the underlying scientific differences are fairly dramatic. GPU3 is more stable, more efficient, and has a larger set of scientific capabilities. We now use OpenMM, our open-source molecular simulation toolkit. We also utilize OpenCL for ATI GPUs and CUDA for Nvidia.
Please see these two blog posts for more information: Prepping for GPU3 release and Open Beta Release of GPU3.