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One of the best ways to create sadness is to make the player feel like they are being left behind. (Although that may not be so good gameplay-wise) For example, a way through to somewhere really great, which the people who have been with you the whole game go through. But then you are suddenly cut off with no hope of getting past. (And worst of all, those people make no attempt to help, as though they have forgotten about you). Hope and not caring are the biggest things that stops sadness

A good thing might be to pretend that it is the ending to the game. Also, reduce the colour saturation as much as possible, so that nothing stands out, and everything looks almost grey. Add in the saddening music, and the player will feel very sad Anyone who has seen the ending to "life on mars" will know what I mean!

Make sure there are no friends (or enemies) left with the player. (Maybe it could be the player themself who has died, and in his last moments is watching his friends go on, to carry on fighting)

I don't think that would work well unless you had immersive devices such as VR goggles and more realistic interface devices.

My brother studied human psychology awhile back, and I think some of it rubbed off onto me... DON'T LAUGH!

Try some "sad" (can't really define this genre) music. This has a better impact with classical instruments and ambient background sounds.

Also try emphasizing the "emotional" body language in your characters, key parts being how the character is standing, the angle of the head, (sometimes limp arms) and facial expressions.

Also build up a character's personality, maybe give them a hidden liking for the main character, and giving them a rather important role in the storyline. Near the end of the game, preferrably the final level, have them save the main character by sacrificing themselves. You could also kill them off or have them leave, but this doesn't have as much of an impact.

Romance is too cliche, so i'll leave that out.

The ending to Outcast was sad and very unexpected.