Well yes, in theory, but it's generally considered in somewhat bad taste to replace fundamental basics of the language. At that point you're not really writing Clojure anymore, it's hard to read other people's code, it's hard for other people to read your code, etc. See the somewhat controversial Allegro CL IF* macro for an example of this (I think that's what it was called; turns out that's really hard to search for).
It's a little different if you're either creating a domain-specific language (at that point you've already made the decision to have a new language, so go nuts) or if you're adding new control structures that you can't have in the base language without excessive boilerplate (see for example the somewhat common AIF macro, which binds its conditional result to a variable). But I'd consider making a new MY-LET macro because I don't like what the built-in LET looked like to be a bit gauche.
Regardless, I just decided to stick with the Lisp dialect that already worked the way I wanted.