Sharing /nix/store via virtiofs is the common case, and the nix store can easily contain hundreds of thousands of files. With the current default (null / upstream "never"), virtiofsd keeps one O_PATH fd per inode and eventually hits the fd limit.
"prefer" uses kernel file handles when available and falls back gracefully, so it shouldn't break existing setups. "mandatory" would also work but requires CAP_DAC_READ_SEARCH.