Indexing was my thought for 2 layer boards.
1) Set up your stand-off holes in each corner of your PCB design.
2) Do everything to get the top layer toner transferred onto the PCB or just stick the top sheet in place (heat resistant clear tape?).
3) Drill pilot holes through the board at te centre of each stand-off. Size to be for a 0.1" male header.
4) Print off the bottom layer.
5) Place bottom layer print onto a block of wood and drill the same 4 pilot holes though the paper/vinyl/laminate.
6) Place 4 off 1x1 headers through the PCB from top layer and turn the board upside down.
7) Place your bottom layer print over the 4 keys to line up perfectly via the centres of the stand-offs.
Stick the bottom layer in place (heat resistant clear tape?).
9) Heat transfer the toner onto the copper via heat press, iron or laminator.
10) Remove both sheets of paper/vinyl/laminate and the 4 off 1x1 headers used as keys.
12) Hopefully a perfectly aligned two layers.
I've not tried it yet but I think it should work?