When layering I think about what frequency range could do with filling out and then adding an instrument that covers that frequency range. I then duplicate the sample with a synth(say for adding a bassline for example) and then layer it(what this amounts to is having a track that mimics the original sample track but only covering a specific frequency range.) Admittedly this is a skill I have picked up after years of training my ears to detect tone and is pretty damn hard for untrained ears. It comes naturally for some people but for the rest of us it does take time.
And hey I also mention adsr,(attack, decay, sustain, release) these are also very important for fine tuning. For example say you wanted to take some tail off a snare and replace with your own reverb. You can have a quick attack, pretty quick decay, short sustain and almost zero release. Your added reverb will sound a lot cleaner after removing some tail from a snare(if the snare has a tail that is) essentially replacing the original reverb tail with your own. << There are far easier ways to do this but I used it as an example.
and not to forget taking off some attack can be a quick way to prevent clicks at the beginning of samples. and adjusting the decay and sustain can be a quick way of removing clicks from the ends of samples.