Is it harder for academics to make fundamental discoveries than in the past? In present day academia, it seems much harder to make foundational breakthroughs than it was in the past. Most work now synthesizes previously discovered results to study something extremely specific. Although this extremely specific thing may be valuable to know, it generally does not have the potential to rewrite the field.

For example, in physics, the beginning of the 20th century saw the revolutionary development of general relativity and quantum mechanics. While there is still much to be learned in modern physics research, it is much more difficult for someone to make large, fundamental contributions to the field, simply based on the fact that the large, fundamental contributions were already made. Now, even an extremely productive researcher may only become well-known in their immediate subfield. Similar notions can be applied to art and a variety of other academic disciplines, in which it is more difficult for one single artist's work to be foundational to the field.

Do academics worry much about the growing insignificance (for lack of a better word) of their work? Or is any knowledge gained worth the effort, simply because the academic enjoys studying the topic (no matter how esoteric)? Any sort of discussion about this concept would be enlightening.
Actually, exactly the same question might have been asked around 1900 when Henri Poincaré ruled the world. 

There is a tradeoff, of course. Some fields get saturated and the seemingly important questions get answered, closing the field in some ways. But those fundamental breakthroughs may open new lines of inquiry. And there is the corresponding effect that other fields open up. Mathematics is like the latter. People today think about a lot of mathematical ideas that didn't really exist historically. 

Whether physics is a fixed field in which everything will eventually be known is, I think, an open and debatable question. I suspect that there will be new ways of thinking about things and thus new and important questions as long as humans can manage to still exist. Quantum entanglement is still pretty "spooky". 

And in the social sciences we may be only at the beginning of what can be known. 

Moreover, each new generation of scientists, in whatever field, starts out at a higher level than their predecessors, and so, have a base on which to reach still higher, with a deeper understanding. Poincaré had problems grokking relativity, as did many of those in his generation. After they started to actually die, relativity came to the fore.