My approach is this:
1) Sub-buss each instrument (i.e. Guitars, Bass, Drums, Vocals, etc.
2) Solo each Sub-buss and just listen. find out which instrument seems to be making it worse. Or, conversely, Mute one sub-buss at a time and see which instrument seems to make the 'Best' impact by being taken out.
3) Work on each one individually to see what frequencies are harsh. To do that, I use a Linear-Phase EQ, such as DMG EQuality (not the EQ you're already using in a track or buss--In fact, "Power" those off.) Using a single band, tight Q, and about 10db of boost, sweep the area you think is harsh and find the center frequency that seem to be the worst. Stop the sweep there, and then
cut that frequency by about 3-6db (or more, if you need). Then, re-enable your normal EQs and unMute/unSolo your busses and see how this goes.
4) Repeat.
You may also add a little "air" up top with an EQ Shelf around 10Khz+ to help your ears.
Everybody else here has some great input. Don't just follow one method. Try them all or even combine methods. If all else fails, if one instrument is still bad, re-track it. I prefer to fix the source than fix the mix, where possible.