It is apparently a condition of the Olympic hosting that the stadium remains first and foremost an athletics (specifically, "track and field") facility. As much as it would be wonderful for Britain to have a "spare" 80,000-capacity athletics stadium, it seems unlikely that it could be filled near capacity for hosting an athletics competition more than two or three times a year at the most optimistic; even two athletics events plus lots of concerts will apparently not cut the mustard. The stadium will be built with an 80,000 capacity, but apparently 55,000 of those seats are expected to be temporary and the permanent capacity is set to be 25,000. Frankly, an athletics event drawing 25,000 spectators is doing well in the UK these days - Crystal Palace has to go some to hold 22,000, the mighty Gateshead International Stadium holds about 12,000 and so forth.
Therefore there has been some discussion that the stadium might be bought, or at least used, by some organisation that is likely to fill it frequently. Premiership football teams have been mentioned as obvious choices - but the requirement that it remain a 25,000-capacity athletics stadium is so inflexible that no Premiership club wants to be in a 25,000 capacity stadium with a running track separating the fans from the pitch. Local Leyton Orient have thrown their hat into the ring, but that's probably more Barry Hearn cheekily getting his 2p in than anything else. (Yet it would make a certain sort of sense...!)
That said, I have had a cunning plan. I think the best possible use for the Olympic Stadium would be for a London franchise in the USA's Major Soccer League.
The Major Soccer League is not currently considered, on a global scale, to be a truly major, er, soccer league. It is known that stars from more established leagues will often go there in the twilight of their career to get a couple more relatively well-paid seasons at a slightly lower level of competition. Nevertheless, if people are prepared to fly around the US to follow an association football team, it's not such a big stretch to imagine that they might fly to the UK for a match. It would certainly raise the MSL's profile very considerably.
There are shades of the old Atlantic League proposal to cream off the crop of the (e.g.) Scottish, Dutch, Belgian, Norwegian and Portuguese leagues to create an unusually top-to-bottom consistently talented league. To take one popular measure of Europe-wide football prowess, the Premiership has 13 teams rated at over 960 points by one scoring system, Spain's Primera Division has 15 such teams and both the German Bundesliga and Italy's Serie A has 9. A counterpart Atlantic League from those five countries would likewise have 9 similarly highly-rated teams.
However, the Atlantic League proposal was always said to be opposed by UEFA, who are highly keen on their traditional domestic leagues. The advantage of a London team (or, less plausibly, one or more Scottish teams...) in the MSL would be that UEFA would surely have no jurisdiction in the competition and it would be down to CONCACAF, who might well be more interested in creative and original solutions for publicity purposes.
There is precedent here in that the MLS is due to expand from being a purely domestic league to an international one in 2007 anyway with the introduction of a Toronto FC team to the previously US-only league. The MSL has restrictions on roster nationalities, but is prepared to bend them for the benefit of this non-domestic team. Might this be repeated for non-domestic teams from other countries? Canada first, possibly Mexico second, then eventually the world?
The MLS would also be a more suitable host than an English league side by virtue of the expected attendance; even if the stadium were to be restricted to a 25,000 capacity, the MLS's current average attendance is around 15,000. It seems likely that more veteran British players would be likely to move to the MLS if they didn't have to leave the country to do so; it would also seem likely that there are 25,000 existing football fans in London who would be prepared not only to support a team in the existing English league structure but also a unified London team, especially if there were some known names in the squad. Perhaps people who will follow England against other countries but do not have a current domestic alignment might also be interested in following an English team against overseas teams?
There is precedent here, in the old World League of American Football, which similarly featured a London team against ersatz American opposition. The London franchise was highly successful for the two years of the WLAF's operation, though admittedly it could not be sustained in the NFL Europe era. (Speaking of NFL Europe, this story about the league's future suggests that expansion of the league is eventually intended, but only as far as eight teams - of which seven seem likely to be based in Germany. H'm! The interesting development there is the plan to license local investors. If this is likely, perhaps this might inspire further expansion in the future should further local investors be found. Might there be even one suitable local investor in London for a suitable London NFL Europe team? Hey, there could be a nice stadium going unused from 2012 onwards...)