The makers of top-performing NICs have been quite good at providing direct user-space access to their hardware, typically by exposing a ring buffer in shared memory, and maybe mapping device registers too, so that the process on the isolated core never does another system call until shutdown weeks later.
It is some hassle to get customers to add boot flags (isolcpus=, nohz_full, rcu_nocbs=, rcu_nocb_poll, hugepages=, etc.), and to put any mapped files in /dev/shm or /dev/hugepages so the kernel won't invent excuses to block the procees, and to direct irqs to other cores; but unikernel setup is probably not simpler.
So, I'm not sure what a unikernel would get me. Portability, or independence from proprietary drivers?