Well yea, of course. I don't put AdSense on affiliate sites, nor would I ever put it on an ecommerce site (although even Walmart and Target do that now).
I dunno how much plainer I can say it. Every keyword in your ad group must be directly relevant to your ad.
So if your ad is for Blue Widgets For Sale, make sure that your keywords are all about blue widgets for sale, and not red widgets for sale, or blue widgets for rent, or just plain yellow widgets, or blue widget maintenance or widget repair. All those other keywords might be relevant to what you're doing, but they're not relevant to the *ad*, so group them into your ad groups according to strict concept.
Even just plain "Blue Widgets" might be too broad (the number one problem I see with client PPC accounts is that they pick keywords that are way too broad) for a Blue Widgets For Sale campaign.
You have to think of the entire process as a kind of flowing path - the keyword leads to the ad, which teases, promises or asks a question that is perfectly answered by the landing page. Any time you veer off that path, you risk losing quality score.