Yes. Of course it can. Ignorance of danger does not make the danger less real.
Hypothetical question: If you make a bad guy the PCs choose to ignore, will you consider TPKing them with antagonist because of it?
Again trying to reframe the point [MENTION=42582]pemerton[/MENTION] is making (or at least how I'm interpreting it, apologies if I totally hamfist this point!), I believe what's he saying is that there are several systems outside of D&D that use character build resources to actively determine the flow of the narrative, and thereby what sort of enemies will be encountered.
For example, in 13th Age, every character spends points to have Relationships with Icons, who are major NPCs within the setting. It is explicitly in the rules that the DM should weave his storyline around the Icons the players select, especially when the relationship dice are rolled at the beginning or end of each session and a 5 or 6 is rolled.
Another example would be FATE, by using Aspects to describe a relationship with a possible antagonist of the player's creation. The Dresden Files RPG, which uses the FATE system, has the players and DM work together in a City Creation session before the characters are created to decide what the primary themes and antagonists of the game will be.
On a slightly different point, I think there is a solid difference between an encountered enemy and a true antagonist. Antagonists are those enemies that the PCs make a choice to continue engaging with throughout the narrative. They are proactive about making choices to strengthen their hand against that enemy and to engage in activities to weaken him.
While it's easy to say the DM chooses the enemy, that's only true in the sense that the DM places the encounter. But the DM already does that for the whole world, since it's assumed that the world has millions of NPCs the PCs could encounter if they so choose. The players have to be the ones to make the active choice that this NPC matters, because they choose to engage with him. Only the places where the PCs choose to spotlight their attention has any effect on the game, and that's just as true of D&D as any other RPG. A BBEG the players choose to ignore might as well be just another Elminster, if the players have no regard for his schemes.