This article was written in response to a request from a student of mine, Dynamics. You can check out his sounds here. I'm just basically documenting my process here, and its a few simple tips and tricks that I use, others may well have different opinions and methods and thats fine. Once you have chosen your melody and the instrument to play it, you may like to follow the below steps and keep in mind the context of your song and what works for you. We'll assume it's a synthesizer in this case but the same can easily apply to a piano or strings.
Step 1: EQ
First, make sure that to what extent is possible, you separate your lead from overlapping with any other elements in your track. Cut all the lows out so that the roll off point of your filter sits just at or below the fundamental frequency of your synthesizer sound. Next do the same to the highs, remove anything above the last / highest partial of the sound so that it doesnt overlap with the percussion and high hats. You'll also need to make a notch around where your snare sits in order to stop them from clashing if applicable. You should end up with an EQ curve that looks somewhat like the following. You could also add a small (maybe 2 to 3 dB or so) boost at the top end of the presence region if you like, so around 4kHz, this will just add a little shine to the sythesizer.
Step 2: Reverb & Delay
Now that we've sculpted out a large chunk out of the sound to make room for the other elements its time to add some content back in. Choosing an appropriate reverb is a big part of getting that thick lush sound for a lead instrument, you want a nice long and dense reverb if you can, my choice is always to go for a convolution reverb, but there are plenty of other types of reverb that will do the job just fine, another of my personal favourites is / was Toraverb by D16 Group which makes leads sound absolutely huge.
Try also adding delay to the sound. Wether this works or not usually depends on the actual sound itself, but it can really add depth to a lead sound if used properly. By this I mean not going overboard and drowning the sound in delay, so play with the timing of the delay and the dry / wet amount. You just want to create an appropriate shadow to the sound to give an appearance of sonic depth. I tend to favour a dry / wet ratio of around 20 to 50 percent. I'd highly reccomend grabbing Dubstation by Audio Damage, it's simply the best delay VST on the market hands down.
Step 3: Chorus and Stereo Widening
Since we've removed a lot of the lead's frequency content, another way to bring back some of that content or make it appear more prominent in the track is to push the sound out in terms of it's stereo width. You can use a chorus effect to do this, which I generally tend to do, but another way is simply to widen the sound. Put a stereo widening tool on the track, and push the sound out to 125% or even 150% of it's original stereo width. Make sure to compensate for the loss of content in the centre of the stereo field by turning the synthesiser's volume up, and always check that the volume sounds resonable in mono as well as stereo.
Step 4: Adding Bite
Finally I like to add a bit of bite into my lead sounds by just using a bit of distortion or a bitcrusher. have it on a low dry / wet value because it will greatly effect the overall volume of the sound. You could even use a character compressor or some saturation for the same purpose, it doesnt really matter what the tool is, the point is just to add a bit of bite and harshness into the sound, because after adding things like reverb and chorus you will have softened the sound a fair bit.
I hope this helps you, and remember that no matter what, if you have poor quality instruments or poor quality samples, this technique wont change that. Neither will it change an uninteresting melody into something interesting so make sure to get these two steps right first.