Intel's iAPX 432. 1975. Instructions were bit-aligned, stack based, 32-bit operations, segmented, capabilities, .... It was so late+slow that the 16-bit 8086 was created.
I thought it was a brilliant design, but it was dog-slow on hardware at the time. I keep hoping someone would revive the design for current silicon, would be a good impedance match for modern languages, and OS's.