[Stephen Colbert]
Thank you. I accept your apology.
[/Stephen Colbert]
Even if you think u r smart and funny at times or all the times, in such easily volatile situations, id probably try something like " hmm... maybe...thats a possibility ( *put on ur nicest smile* ) / .... but the point im trying to make is… "
Now practice this in front of the mirror until dawn tomorrow.... and again.... put on your nicest smile. :)
Saying something like " There`s no guessing about it" or “Yeah, I know” or something along those lines is only going to piss people off unless they know u well.
“Honesty has its priviledges.”
“I used to work for NASA. How about you?”
<loud, guttural belch>
We have a winner!
“I guess you think you’re smart.”
“I don’t have to guess. I know I’m smart.”
“I guess you think you’re funny.”
“Sorry if you’re having trouble following along. Would it help you if I held up a sign telling you when to laugh?”
My former boss actually asked me to do this. I guess I should be relieved that she didn’t demand a laugh track.
Vinyl Turnip: 
“I bet you think you are smart, don’t ya?”
…
…
WHORE!!!
Or as another alternative:
“Yeah, don’t you wish you were?”
There are lots of funny, snarky suggestions here, but I truly was hoping for something that can actually be used to defuse someone’s hostility, not inflame it. I have no difficulty thinking of wiseass responses. Sigh. I am the uncrowned Queen of Wiseass Responses. I often come up short when I try to think of diplomatic, kind, graceful things to say, though.
Excellent. I’m a big fan of politely asking people to explain their nasty remarks. It really throws them, and it’s much more effective than trying to out-nasty them … .
I can’t believe no one else posted this yet:
“I guess you think you’re smart.”
“No, but I did sleep at a Holiday Inn Express last night.”
Someone emailed me to suggest that I respond to “I guess you think you’re smart” by saying “Ah, well, as Cicero said, trahimur omnes studio laudis.”
The person who emailed that to me is a wiseass. But I like her thinking. 
Reminds me of the “Not The Nine O’Clock News” sketch in which Gerald, the talking gorilla, starts quoting Aristotle - in Greek.
When someone says something like that, I play psychologist. Just nod and say, “How do you feel about that?”
When someone whips that question out on me, my inevitable response is: “I don’t feel; I think [insert opinion here].”