I didn't consider GPU's precisely for the reason you mentioned – because of their unsuitability to run sequential workloads, which is most applications that end users run, even though nearly every modern computing contraption in existence has them today.
One, most assuredly, radical departure from the von Neumann architecture that I completely forgot about is the dataflow CPU architecture, which is vastly different from what we have been using in the last 60+ years. Even though there have been no productionised general purpose dataflow CPU's, it has been successfully implemented for niche applications, mostly in the networking. So, circling back to the original point raised, dataflow CPU instructions would certainly qualify for a new design.