Assuming familiarity with regex, is there ever any reason to use the normal incremental search (C-s) over regex (C-M-s)?
@Dan provided a good answer to the question. I will add this:
As @Adobe indicated in a comment, you can use
M-r anytime during Isearch (literal search or regexp search) to toggle between regexp search and literal search. Easy-peasy.
This means that it can make sense to start with whichever search mode you expect to use first, or most, and just toggle to the other as needed.
What's more, literal Isearch is not so "heavy maintenance" as regexp Isearch: what you type is directly and immediately what you get. So generally, yes, I would say that it makes sense much of the time to start with