Whenever the problem happens it will always be working the night before lol ;) :p

It could be a problem with a digital to analog converters, which would mean the output is not driven out the thing - this is what happened to mine.

Have you tried outputs other than the main 1/2 outputs ? If you go into your windows control panel and then into your sound options you should be able to change your default output to another pair of outputs like 3/4, or 5/6 etc.

In all honestly I hate my Saffire card, the routing options are too much of a pain in the neck... the headphone outputs share the output 1/2 signal path so monitoring output from other channels means you need to start mixing the channels and you loose channels when you do that...

I am getting rid of mine soon and getting a Motu 828mk3