Different sections draw different readership, so you can target your ad to your market. Too many papers dilute the market. Bigger ads can overshadow your small ad. Your ad can get lost in the clutter in larger papers. Your ad may be grouped with competitors.
Testing is the way to go.
Some of my clients have had good success with the TV Listings section, some with the business section. Negotiate good placement in the paper and good placement on the page. Sundays are not as good as weekdays for smaller ads because they can get lost. Wednesday is coupon day, which has high female readership. Don't forget local weeklies and classifieds.