For me S-expressions feel like the most natural way to program because they compose naturally with zero ambiguity. Infix notation might be slightly clearer for simple expressions but it doesn't compose: As soon as you try to compose infix notation you have to add parens, depend on unstated precedence rules, or both. Lisp's philosophy is to just use parens everywhere, make everything composable, and have no precedence rules.

That said, I would hate to write Lisp code with Notepad. Fortunately nobody does this. In conjunction with a paren-matching, auto-indenting programmer's editor (which is roughly all of them these days), S-expressions are easy. A good editor is vital not just for writing Lisp programs but also for reading them.

I will not claim parentheses are mandatory. I find Haskell just as simple, unambiguous, and composable without (many) parens but that's only because it has automatic currying, and that takes a bit of practice to wrap one's head around.