Best way to use miles on a 2 leg flight?

So looking at flights to Nashville this will mean London to Atlanta on a virgin flight then onto a delta.
Can I use miles to upgrade on the virgin part , Or use a combi fare?

This largely depends who you book with and who your miles are with. Presuming you are making this a return from London all the way to Nashville and not 2 separate bookings:

If you are booking through VS and want to use VS miles then yes.
If you are booking though DL and want to use DL miles then yes.