I'd say the crucial factor is the lead tone must be differentiated from the rhythm tone in a way that makes it clearly distinguishable from the backing.
That means, for most practical purposes:
- more volume
- more FX like reverb or delay to create a 'space' for the sound in the mix
- often more biting/cutting tone
- often more compression and/or sustain
- often more drive to allow for single strings to sound stronger in leads
It doesn't need to be all of these. For instance, over a pretty bright backing a dark, thick Les Paul neck pickup legato lead might work wonderful, but it's got to have the FX and the sustain to stand out.