Arguably, the biggest thing about S2D is that the solutions currently have to be certified (see this bit of documentation from MS for more detail). This obviously doesn’t really affect, say, virtualized versions or ones up in the public cloud such as in Azure in a meaningful way, but it’s still technically a requirement much like logoed hardware for Windows Server supportability. Anyone want to point me to the logo stamped on your VMs? Didn’t think so. Now, from a pure FCI perspective none of this is an issue. The way a Windows Server failover cluster (WSFC) is currently designed, it is expecting that all nodes participating in the WSFC are also using/needed S2D. Why am I mentioning this? Disaster recovery.
It shouldn’t stop you from moving forward with S2D, but means you’ll probably have a bit more research on your hands.