Perhaps you've heard the term "streaming" when reading fantasy football content this summer. What it means, in its simplest form, is starting a different player in a lineup slot each week based on matchup. Typically, because rosters will only start one quarterback and tight end, these positions are stream-worthy, and are easily attainable each week off the waiver wire.
Don't keep something that is easily replaceable. Never keep a defense or kicker, for instance, (unless you have a very unique league where defensive scoring can be worth as much as a top skill player), and think long and hard about keeping quarterbacks and tight ends. The thought here is that many quarterbacks and tight ends see little point differentials on a weekly basis. So for every Matt Ryan and Kyle Rudolph, there's a similar player you can snag in a similar round in your draft or similar dollar value in your keeper auction.
Of course, if you're able to lock up a potential star for more than one year as a keeper, that proposition may be a different story. In general though, focus your efforts on skill positions like wide receiver and running back.