There is a lot of investment in this area, and the "state of the art" is changing rapidly. While my answer is reasonable today, that may change over the coming few quarters.
The biggest performance issue will be latency: latency to the memory, latency to the interconnect, and latency to the file system. Bandwidth is also an issue, but not nearly as noticeable as latency.
The next biggest performance issue is the lack of support for "common" HPC technology like DMA/RDMA, GPU's, and other hardware accelerators. While not every cluster will have these, if you are accustomed to the performance gains of these kinds of technology the VM environment will be that much worse by comparison.