Of course if its an accident or bad timing that turns a six player group down to two, then this will also need to be discussed with the players too. have had experience of running games with reduced player numbers in the 7th Sea campaign setting, and in both instances the experience was different. Essentially the game can go one of two ways. (a) either one or both characters take the lead in creating their own story and entertain themselves with the GM acting as the 'bounce' or (b) where the GM entertains the players and has to be prepared to burn through tons of material each session. If found the best way is to announce to the remaining players of the situation and ask them what they wish to do. Carry on with the story (b) or (a) create their own little private adventure to laugh about while the other players have gone away. I find (a) can be very self indulgent and hard to bring to a satisfactory conclusion, but (b) whilst serving the story, prevents the other players from learning of the plot movement, but its the amount of written material this can get through. One way to avoid this is to slow the pace down and become more descriptive.
In a two player designed game, both the characters and adventure needs to be tailored to the players and GM, whereas an unexpected two player game will require careful amendment to the adventure to ensure they don't get caught out. I.e. a big fight suddenly becomes a sneak and hide session.
One final observation is when a small group of a DM and two players (especially those two who have decided to multi-class and thereby reduce the speed at which they progress their character) expands to a larger group, usually through invitation etc, suddenly these multi-classed characters will fall foul of the other players who rise rapidly through the levels and have the potential to overrun the main original two heroes.
There is a final 3rd variant to this, which I do not recommend, I have tried it once and it didnt really work (oddly I love Ars Magica for this very reason, and my own developed Dune game uses this a foundational point) which is whereby each player has 2 or more characters, either as part of the party of as secondary or supporting characters in other locations.
