The low end is different enough between the V6 and V8 to be noticeable, particularly when you load the vehicles up.
You're gonna notice that the V6 will drop mpgs rapidly when you throw 33's, a bumper, and some other goodies on it; not to mention it will need to rev higher just to lug all that weight around. The V8 on the other hand can bet stretched a bit further without needing to regear, additionally you're also looking at other things that are beneficial (All-Time 4WD, 5-spd Transmission if you're buying older than about '05, ect.).
The V6 4th gens are good vehicles, but I still laugh at most anyone that is picky about mpg for this type of vehicle; if you're that concern about fuel mileage you will more than likely be better off with a Highlander rather than the 4Runner. Now stock for stock, unless you're towing, the V6 isn't a horrible choice of engine (I would have gone with it had the S10 Blazer I had not turned me away from anything less than 8 cylinders due to it's horrid early 4.3L).
This is a vehicle you buy for capability and reliability, mpg is the cost you pay; particularly if you mod them. I'm running 35's, full under armor, 3" suspension lift, 1.5" BL, and full metal front bumper; I'm still pulling about 12mpg in town and about 14~15ish freeway. That's rather appalling to most people I suppose, but the low-end still feels torquey (despite a significant increase of 0-60secs from about the factoy 7.7 to close to 10 seconds), the V8 still pulls hard and I have towed a trailer and yanked 2 4Runners at the same time for recovery with my vehicle. I've been in a 4th gen that was ridiculously overloaded in terms of weight (at the time I believe he had 39's on his 4th gen?) with a V6 and that thing had a hard time getting out of it's own way; got a bit better when he regeared it, but still needed a bit higher revs.
Bottom line, if you're quibbling over 2mpg difference in this particular segment, then you're more than likely not going to benefit from this vehicle and would be better off in a Highlander or similar vehicle. V6 or V8, just adding slightly more aggressive tires of the same size will nick your mpg down; it won't matter on the engine you'll be disappointing because you're focusing on the wrong thing.