Going through it all just once has more benefits than just speed. Imagine for example, that you have to replace every occurrence of "A" with "B", of "B" with "C", and of "C" with "A" — thus swapping places. That's extremely easy if you do it in one go, and quite impossible to do it in three iterative substitutions.

Good:

%replace = ( A => 'B', B => 'C', C => 'A');
s/(A|B|C)/$replace{$1}/g;
[download]

Bad:

s/A/B/;
s/B/C/;
s/C/A/;
[download]

For the latter, everything that was "A", "B" or "C", will now be "A".