Blue you get from a chest. Pretty easy in the Act 3 since it's likely the alternative relic is trash by that point. Green is the buffed elite. Again pretty easy in Act 3 because if you can't stomp it you're definitely not beating the heart anyway. Red is forgo a rest stop, which can be done anytime but I usually do it before the boss, especially if the boss is Hexaghost, because why both resting just to buff the boss?

> Technically the green key only calls for an extra challenge in facing a buffed elite instead of sacrificing, at least in the latest version.

I don't know if the latest version changed this, but the green key was definitely also a sacrifice -- if you look at the map, paths that allow you to get the green key have one less fire.