Isn't it insane how much Otacon and Snake change throughout the series?
They start out as complete opposites: Otacon, a nerdy mess of a scientist, panicked, terrified, oblivious and heartbroken. Snake is practically a hero by the time they meet, and only proves it further by saving Otacon's life. His presence pushes Otacon to become braver, clean up the mess he's created and assume responsibility for it. In the first game, the power imbalance is pretty strong: Snake is confident, powerful and bold. Otacon learns he can be just the same by doing what he does best and providing backup for Snake, and he grows to become not only a better, stronger person emotionally, but also become Snake's equal, like we see in the second game.
MGS2 is like the honeymoon: they have full trust in each other, know how the other thinks and works, how best to provide for each other. They're both extremely confident in their skills and know what the other is capable of.
However, honeymoons always come to an end, and MGS4 gives us a broken shell of what their relationship used to be. Snake is distant, he's alone, but on purpose. Otacon is constantly worrying, always struggling with his feelings of sadness and his wish to be useful to Snake, grant him the rest and peace he deserves after so many battles. Snake, however, would rather be left alone instead of (what he believes is happening) pitied.
The distance is so easily felt in the many cutscenes of the game: not only the distance that separates them when they speak over the CODEC, but also the emotional distance that is clearly there in the scenes where they are together physically. The moments of awkward, silence, heavy with sadness and the way they almost fear touching each other quickly become obvious when paying attention. The novel expands upon this, citing many moments where Snake voluntarily ignores Otacon's worries, notices how sad Otacon is about his situation, and where Snake isolates himself because he can't bear hurting the people he loves any more than this. His newfound cynicism is what he uses to protect the others from what he's become, a ghost of the hero they all thought he was.
It's clear: Snake's overwhelming shame and guilt is what makes him unable to communicate with Sunny, who doesn't know how to act around someone so distant, Meryl, who used to love the 'legendary hero' Solid Snake, and most of all, Otacon, who doesn't care for the hero, but for David, who has to bear the world's weight upon his aged shoulders.
It's in their inability to communicate properly that you can feel just how much they care for each other, and it's what hurts the most.
WARNING: HEAVY SPOILERS FOR MGS4