I think the key to making a character tragic is to make sure the reader CARES about them. Make them a bright point in the story and then murder them, or make them suffer. Maybe have them keep their upbeat attitude, even right until the final moment when they die/break/become mutated into something horrible.
But the key is to make the reader care about them, make them like the character. You can lump as much nastiness on the MC as you like, but if you have support characters they MUST have some bright moments, or they're just an extension of the MC's problems, not really characters at all. If they face trials like the MC does, the audience will probably just be overwhelmed with the misery and burn out on the story so the side characters are where you lighten things up, keep the audience hooked - and then USUALLY smack them down. Maybe give a few of the side characters happy endings as the MC leaves them behind, just to keep the misery from ruining everything.
