I could hold the whole 6502 instruction set (and their cycles) in my mind while programming, it was that simple.
I acquired a Z-80 softcard for my Apple ][ (for trying out CPM) and was flabbergasted by the expanded register set, the complexity of some instructions (e.g. DJNZ) and the fact it ran at 4MHz vs 1MHz for the 6502 (got a speed demon 65C02 card later). However I couldn't keep all instructions and timings in my head. Speedwise the 1MHz 6502 and 4MHz Z80 were on par. I preferred, however, the fact that I/O was memory mapped on the 6502.
A few thoughts:
> the complexity of some instructions (e.g. DJNZ)
Well, of course the idea of DJNZ was to implement a very common pattern (decrement a register and jump (normally backwards) if the result was not zero) - this tended to simplify code rather than make it more complex.
> However I couldn't keep all instructions and timings in my head.
I was never really interested in the timings, but I did get to the stage (not by conscious memorisation) of being able to assemble and disassemble Z80 code in my head, with some accuracy.
> I preferred, however, the fact that I/O was memory mapped on the 6502.
Many (most?) Z80 systems used memory mapped I/O. It's down to the hardware designer.