Well, from how I sit on most issues P&T tend to pretty much line up with where I feel. But one of the bigger things I have to call them on is when they tried to prove/show that Hybrid cars are impractical for the typical family.
To show this they matched up two lesbians (a hot one and the "typical" masculine/dyke one) gave them a Prius and sent them on a "date" that involved a couple-hour drive outside of Las Vegas (or L.A. I forget some of the particulars.) The car was loaded with what the show reckoned a family going on vacation might need if they also had children. So, in other words, the Prius was loaded with some luggage and baby junk.
Post-trip the Prius managed to get somewhere in the high 30s or low 40s MPS which the Butch Lesbian said was about what her gasoline-only compact car got. Penn and Teller's argument was that the Prius just makes people "feel better" without doing much real good as the car is more expensive than a gasoline only-car, offers no meaningful benefit to MPGs and is impractical.
Unfortunately this was one of only a few times I had to call BS on them. The Prius isn't supposed to be for these type of applications! Of course it wasn't practical for a vacation drive and didn't get stellar MPGs on a mostly highway trip. In fact that's the entire point of the damn car! It's for commuting! It's for getting around town! You're not supposed to load it up with luggage and kids towns and drive 200 miles out of town. You're supposed to putter around town with it which is why it's City MPG is better than the Highway MPG (as opposed to gasoline cars where the opposite is the case)! Pretty much everything else they said in the episode was more-or-less good (including a support of Nuclear Energy, the Yucca Mountain disposal location and how safe it "really" is compared to 40s and 50s news reels.)
But they really dropped the ball on their "dis proving" the usefulness of Hybrid cars as they tested the hybrid car in the one situation where it isn't designed to perform better.
(Also, oddly, in this episode they wondered what you do with the car's batteries when they're used up since they'd pose their own danger. This being the same episode where they supported chucking nuclear waste into a mountain and just forgetting about it.)
A vast majority of the time, however, I mostly agree with what they have to say though lately the "sensationalism" of how they go about it and the gratuity of their use of curse words (which I've no problem with) and naked women (which I really have no problem with) has increased. But rational me is also able to disagree with some of what they say.