As far as tone it really matters what the song is and what guitar I'm playing. My basic approach is to keep the tone and presence fairly close to each other and they tend to be on the higher side of my tone settings. The bass I usually start off around 1/3 of the treble and then often I bring it up depending on how it sits with whatever mix I have. The mids often fluctuate the most, almost as if they define the character of the sound. (I hate to use 'voice' here, but in a sense the mids basically address that for me)
I rarely use any modulation fx on leads, the one song I have that possibly I did use modulation on the lead is The Whisper which was very clean tone wise. I prefer modulation on rhythm parts where it embraces the mix.
Delay is usually somewhere between 300-450 ms with a little feedback and I prefer ping pong. I do sync it because I can and I think it's less distracting.
Reverb is set to where it just sounds a little wet unless it's a very clean piece, then I'm apt to bring it up some.
Pretty much my philosophy on lead is that it needs to cut through the mix, subtle things (like pinching the string in different places for different squeals) are much better done through my playing. Adding feel to a lead with a lot of fx is fine sometimes, but I find that 'feel' is much more genuine when it's impromptu...
