This depends heavily on the context. In The Art of Computer Programming, the analysis of algorithms is done in terms of machine code. On the other hand, the proverbial centipede lost its ability to move as soon as it started wondering about how it moves.
I tend to think you should be able to go back and fourth between mental models. Like obviously when you're thinking through how to set up business logic, you should not be thinking in terms of registers and memory layouts.
But when you're considering two different architectural approaches, you should, at least in broad terms, be able to think about how the machine is going to execute that code and how the data is roughly going to be laid out in memory for instance.
