Keep your friends close and your enemies closer. Louisville may have been awarded the No. 1 overall seed over top-ranked Gonzaga after surviving the big East gauntlet, but the Selection Committee gave Pitino’s Cards no sense of security in the same region as college basketball’s primo programs.

Duke and Michigan State would be the worthiest of adversaries in a Final Four. Instead, Louisville may have to dispatch one of these nemeses before they reach the Georgia Dome. Louisville’s swirling defensive pressure is their hallmark and they’ve laminated themselves over opposing offenses like Mike Tyson’s face tattoo.

In addition to their suffocating full-court press, U of L’s guards and forwards have been expertly trained to anticipate passing lanes like cornerbacks and create deflections. Senegalese center Gorgui Dieng is a shot-blocker who puts a lid over the basket he’s defending, and as a whole, Louisville allows the fewest points per 100 possessions in the nation.

Duke is the antithesis of Louisville. Mason Plumlee has been the best center in the nation this season, but the Blue Devils are 18-1 with hot-shooting stretch-4 Ryan Kelly in the lineup.

The Blue Devils are deep in scorers at the guard position but Rasheed Sulaimon, Seth Curry, Tyler Thornton and Quinn Cook lack a certain grittiness on the defensive end. They can slap the floor all they want, but there are no Shane Battiers or Nolan Smiths in this rotation. Defensively, the Blue Devils don’t fit the profile of a national champion and perimeter defense is their Achilles’ heel. Even more disconcerting is that Plumlee, one of the nation’s most prolific rebounders, is crashing the boards solo. Duke is 322nd out of 346 teams in rebounds per game.

In the Round of 32, Duke could face the quintessential stretch-4 in 7-seed Creighton’s Doug McDermott. McDermott looks like a rec baller in his tall T and elbow pad, however, the overlooked Creighton junior is already a two-time All-American with an uber-efficient scoring arsenal.

He’s the only Creighton scorer putting up double-digit points, but he can score in a bevy of ways. In the first round, McDermott will have to overcome Cincinnati’s bludgeoning defense. The Bearcats are an old-school Big East defense that is ranked 26th or better in opponent points per game, field goal percentage and seventh nationally in blocks. Creighton isn’t the only mid-major threat in the Midwest either.

Fourth-seeded Saint Louis honored the late Rick Majerus by outlasting VCU and Butler for the A-10’s regular season and tournament championships. Butler’s Brad Stevens believes Saint Louis could win it all.

Sixth-seeded Memphis is the only team beside Gonzaga in the tournament that went undefeated in conference play. Michigan State has remained under the radar for much of the season, but assuming they take care of business, Izzo and Coach K will square up in the Sweet 16.

The Spartans physical frontcourt has been trumpeted throughout the season, but guards Keith Appling and Gary Harris are filling it up on offense. Besides those two, there are a slew of other guards who can play spoiler in the tournament. Missouri’s Phil Pressey is one of the best distributors in the nation, and Oklahoma State’s Marcus Smart will be auditioning for NBA scouts on the tournament stage.

Meanwhile, at the top of the bracket, Louisville and their one-two combo of Peyton Siva and Russ Smith will be watching. Louisville’s path to the Final Four isn’t as unencumbered as Gonzaga’s in the West, but ultimately, if they survive this region, they’ll be hardened by the experience. There will be blood, bruises, sweat and tears, but when it's all said and done, Louisville red will run through the streets of Georgia at the Final Four.