When you are developing games, sometimes.
When you are developing most other applications every byte does not matter. What matters much more is overall system architecture, collapsing unnecessary abstraction layers that some developers (especially java developers) seem to love and optimizing your datastore access.
As always, profile profile profile.
A company I worked for spent a violent couple of man-decades flipping our proprietary scripting language from interpeted to bytecode generation, obviously with tons of bugs and subtle semantic changes, and it ended up boosting overall system performance by about 30%. We could have done nothing over that period of time and hardware advances would have made a bigger impact.