In The Old Man and the Sea, who is Santiago's enemy?

This is a very deep question. I don't think that this
novel necessarily has an "enemy" in perhaps the sense you are talking about. There are
certainly no direct antagonists who try to stop Santiago from achieving his goals. We
could say that the fish would be the closest thing that we have as an enemy. The fish of
course is desperate to avoid capture, and seems to match Santiago's resoluteness
and stubbornness with his own determination to escape. Note how the fish tows the boat
for two days before he admits defeat. However, the problem with regarding the fish as
the "enemy" of Santiago is that both his struggle and his defeat are matched by the
struggle and defeat of Santiago. In the fish's demise, Santiago himself "fails" in his
struggle, as the fish is lost to the sharks. Both the fish and Santiago in their own way
are dejected and defeated.

Perhaps it might be more
accurate then to say that the real "enemy" in this novel is an indifferent universe that
gives little weight or importance to our momentous struggles. Santiago feels completely
"beaten" by forces beyond his control, and in spite of giving his all into the struggle,
admits defeat:

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He knew he was beaten now finally and without
remedy and he went back to the stern and found the jagged end of the tiller would fit in
the slot of the rudder well enough for him to steer... He was past everything now and he
sailed the skiff to make his home port as well and as intelligently as he
could.

Perhaps, then, if you
are looking for an enemy we need to think about the indifferent universe as the biggest
opponent of Santiago, as he struggles to make meaning in an immense, impersonal world
and refuses to allow his own human spirit to be dwarfed, even by
defeat.