If you live in a "safe" state (CA, WA, ...), where one of the two big candidates is effectively certain to win, you can vote for your first choice third-party candidate in a way which might help in the long run -- once e.g. the Libertarian Party gets 5% of the vote in an election, it gets federal matching funds, and will be a lot harder to exclude from the process.

In the long run, I think I'd take the worst of the D/R candidates over a string of 8 consecutive elections if the consequence is ending the two party stranglehold.

The way the system works, without proportional representation, you probably will ultimately end up with two parties, but I'd rather replace both current parties with new competent-but-ideologically-distinct parties (like, say, a Green/Socialist/Union/Interventionist/etc. party vs. a Libertarian/Free-Market/Business/Isolationist party).