I think we can still make a positive difference by working to deny the duopoly legitimacy. If a quarter of voters cast ballots for other races and either vote for non-Demolican presidential candidates or just don't vote in that race at all, it would send a healthful message.
I'm promoting the idea of pairing disaffected Dems and recalcitrant Reps who would otherwise hold their noses and vote for R or O, and having them pledge to each other they'll use their votes to follow their consciences instead. They would ordinarily cancel out each other's vote, but instead they cancel the major candidates and use their votes constructively. Most importantly, they don't give the appearance of supporting the status quo. See VoteBuddy.com.