The biggest factor would be if the existing parties at some point fail to absorb a political movement in substantial form that thus requires it to go outside of the existing tents, but that typically just reshuffles the deck chairs and you end up with a new party system with one of the old ones splitting between the new party and the older former competition (basically what happened in the 1850s).
What stops that from happening now is that national parties' apparati have become very good at finding new sources of discontent, buying them out, and astroturfing the whole thing.
Republicans have been very good at assimilating new movements but Democrats still think new movements need them more than the Democrats need the new movements.
That's where the next big potential reckoning of the system could be. The economy has been to this point unfair but there has been opportunity out of the sheer length stability and growing scale. Now that the economy is bad, there's opportunity for either the groups on the left to be the origin of a new successful party, for the Democrats to absorb them, or for the movements to abate
If there's a V shaped economic recovery, I could see the far left mellowing out like they did in the 90s and the entire thing not happening. If the economy doesn't come back quickly and Democrats still perform poorly, that makes things more interesting.