I'm building a minimal instruction set computer, and the humongous size of ROM just bothers me a little bit. I think a 4/5/6-bit computer is much more practical, since half of the ROM will be instructions, and I surely don't need more than 64 different instructions. My current project only uses 4 instructions, actually: two instructions to transfer data between the 12 registers and the accumulator register, one instruction to manipulate the flags, and one more instruction to perform conditional jump. I decided to use 4-bit word size and just use two registers if I need 8 bits, or I can just do multiword operations in software.
As of size, bigger often means slower, since you will often need to run long wires with tons of repeaters.
