I tend to use the same tone to avoid phase problem when using pod farm but in a reamping situation I'd probably dial two different tones with different heads if possible! You can listen a clip here https://soundcloud.com/#guillaume-tanguay/draw-the-line-export-vocals same tone for rythms and and lead but with delay and reverb!
Yes, always! I know most of the guys here use pod farm/amp sims etc. I mostly go with 2 amps for rhythms (5150/Laney blkhrt mostly) throguh 2 cabs (orange(back)/randall). Leads are mostly Green channel on the 5150. Gives you a real nice lead tone (that green channel).