[I've decided to weigh in even though I am neither particularly experienced in mathematics or pedagogy. But, now feels like a good time to procrastinate from work...]
It is possible to learn reasonable chunks of 20th century mathematics without knowing what a derivative is. For instance, let's take abstract algebraic geometry: most of Grothendieck's theory (as developed in EGA/Hartshorne) requires several prerequisites (sheaf theory, homological algebra, general topology, commutative rings) but notably not calculus. An advanced undergraduate (who has studied all this and much more) once told me he did not know the definition of the exponential function. You might object that general topology grew out of foundational questions in analysis, which in turn grew out of calculus; however, one can define the requisite notions (topological spaces, continuity, connectedness) from first principles. There are in fact essentially no prerequisites for starting general topology, interpreted suitably. Similarly, abstract algebra can be studied from naive set theory, starting with the definition of a group.
Now many of the important results in algebraic geometry do rely on analytic methods; to pick one example, the Kodaira vanishing theorem can be phrased as a purely algebraic statement about smooth projective varieties over a field of characteristic zero. But the usual proof uses complex analytic methods (Hodge theory), and calculus is certainly a logical prerequisite for them. Nonetheless, let's say that you wanted to shun every part of algebraic geometry that depended on analysis; there is still plenty of interesting stuff to think about.
(Maybe Kodaira vanishing is not the best example: Deligne and Illusie apparently found a purely algebraic proof, but only several decades later.)
So does it still make sense to know calculus? I think the answer is a clear yes even if you fall into the hard-line category above. More generally, it helps to have an awareness of the historical context of ideas.
Mathematics tends to be heavily cross-pollinated: ideas from one field fertilize another. Many of the greatest ideas in one field are inspired by those of other fields, even if in the final product (the polished version that appears in papers or textbooks). I was recently reading a paper on number theory that claimed to be inspired by an argument of Witten for the very non-number-theoretic Morse inequalities.
Here's an example: there is a notion (as Pete Clark mentions) of a derivation of an algebra: it's a map that behaves like ordinary differentiation does, i.e. satisfies the Leibniz rule. It's entirely possible to define a derivation abstractly and memorize the definition as such, without understanding where it came from -- of course, calculus -- and work with it.
In fact, it is possible to treat any mathematical idea in this way -- as a purely self-contained, isolated concept. But most of us (certainly including myself) would instinctively recoil at this.
In general, when confronted with a set of axioms, one asks why they are there. Anyone can dream up a mathematical structure, but only some are interesting; those that are interesting usually are because the axioms are intended to model some idea. For instance, groups model symmetries or transformations of an object. If you are aware of this, then the idea of a group representation becomes more intuitive than if you think of a group exclusively via its literal definition as a set structured in a particular manner.
Mathematics, historically, has not proceeded from the general to the specific, but from the specific to the general. (And back to the specific, sometimes.) Projective and affine varieties came before schemes, $\mathbb{Z}[i]$ came before general Dedekind domains, and integration in euclidean spaces came before modern measure theory. "Categories" may be foundational material, but they were invented to better understand algebraic topology -- a well-established discipline by then.
It is of course impossible to learn mathematics in historical order; there is not enough time in one's life, and often there are shortcuts one can take to understanding classical material with a better modern understanding. But if you want to understand and work with the axioms in modern mathematical structures, it seems only natural that you should have some awareness of how people decided to put them in.
(In fact, in all the above examples, the axioms for the relevant modern structures (schemes, measures, Dedekind domains) are precisely those intended to model the essential features of the classical examples.)
In short: it is possible to treat mathematics as solely a game played with meaningless marks on paper, devoid of history and culture, in which case ignoring something like calculus is probably feasible, at least if you stick to the appropriate subfields. (Apologies to David Hilbert and Zev Chonoles: neither endorses this approach, but I have to pick on the quote.) But this seems to me neither a sound approach nor a satisfying one.