I see 3 different ways to go here.
The first is taking the best veteran defensive player available, someone who has proven over time to be an impact player every year. The upside is elite play is a certainty, but the downside is that the player may only be elite for 2-3 more seasons.
Top Choice: Champ Bailey
Others to consider: Ed Reed, Brian Urlacher
2nd option is to take the on the rise defender who's played 3 or fewer years in the league. The upside is that you get a guy still on his rookie contract who has many years of his best football still to be played. The downside is the NFL has had a ton of players have 2 great years, only to fall off dramatically later in their career.
Top Choice: Patrick Willis
Others to consider: Mario Williams , Antonio Cromartie, DeMarcus Ware
I actually would rather have Williams, but I believe Willis would fill such a huge need on this team for speed at LB.
3rd option is to take someone who takes the offense to a point where they simply cannot be stopped. The downside is that the defense or special teams could still lose the game.
Top Choice: LaDainian Tomlinson
Others to consider: Antonio Gates, Adrian Peterson, Jason Peters