This means two things.
1. To create a masterpiece in the arts or sciences or any other field of human endeavour.
2. To unite with the Source.
One is a noble pursuit. You can respecify this to mean fully engage with the faculty/will/purpose of the being that you are and 'work' it towards virtue or excellence and abide in the happiness that this brings. This may be as simple as hunting. You are a hunter. You are built for hunting. You have great eyes and an peerless aim. You are passionate about the hunt. Now work it. Hunt. But not only hunt - hunt with virtue, take that crack shot, catch the biggest sea bass - aim for excellence. If you are 'a Jack of all trades and master of none' that Jack can still create fusion between disciplines and pull off incredible acts of Jackness.
The second one works very well with the first. Uniting with the source implys being conscious in and of the moment simultaneously. The source is consciousness (not necessarily a specific consciousness). Those who are more present in the moment will typically work greater acts of virtue within the context of their will. This applies to everything from cricket players to catholic priests.
Therefore the Great Work is undertaken through knowing thyself and supporting that knowledge with exploration of one's own being until one finds Will. This almost always converges with restraint on desire and the accompanying discipline. It is also taken through meditative practises which focus on being present. Yoga teaches all this as do many other disciplines.
The Great Work is Will x Virtue = Happiness
Having completed the Great Work is impossible. The Great Work is an equation, an engine, a machine. It is doing. It can't be started until one is present of their own consciousness and will. If you make the Great Work into the journey to it (I have 50% of the Great Work, 75%, 100% yay! I have completed the Great Work!!!) rather than the journey through it I believe you are decieving people and unnecessarily prolonging the initial phases. This was one of the problems that Opus had with the WMT at the beginning of his early work (with K and C with the HGA if I remember correctly). The Great Work is not about working towards the Great Work, its about doing Great Work.
Opus does not have to meditate himself out of existence in order to do Great Work. For those of a certain type of will, for instance metaphysicians, thinking onself out of one's own existence would imply a virtuous act as its a really difficult and challenging thing to do which requires serious will and skill. A dancer does not have to do that in order to be happy. They just have to be involved in awesome dancing if dancing is what they are. They will be happy.