In essence what makes a signal or even Asynchronous in a digital design

For combinatorial blocks, if the inputs are all driven by the same clock, the output will be timed by timequest (in Quartus) and can be considered synchronous. For most cases, if you are using signals on two different clock domains, the output is asynchronous to any clock and needs to be synchronized appropriately.

Flip-flops can normally be considered synchronous in your design. Timequest handles the time delay associated with flip-flops.

If you have a signal locked to the same clock, but in a different phase, I do not consider that to be asynchronous. The care you must take is the setup and hold times with respect to the rising (or falling) edge in your design.

I'm sure others can give a better explanation on asynchronous vs synchronous, I figured I'd give it a go.