Romero, joint overnight leader alongside Australia's Cameron Percy, collected nine birdies in his second round, the only blot on his copybook coming with a bogey on the par-three eight hole.
Scott Brown of the United States was Romero's nearest challenger after a stunning 63. An eagle at the par-four seventh was the highlight of a round which was spoiled only by a dropped shot on the par-four 14th.
Brown's fellow Americans, Peter Uihlein and Steve LeBrun, were a shot further back on 12 under after both followed up opening rounds of 67 by matching Romero's 65.
Uihlein, starting on the back nine, surged into contention thanks to a run of six birdies on nine holes from the 12th, while LeBrun gave himself some momentum by picking up four shots over his first five holes.
Percy did not fare quite so well as his overnight co-leader, but stayed in the hunt with a two-under 70 to secure a share of sixth place.
Romero's compatriot Fabian Gomez was three strokes off the pace after a blemish-free 64, with fellow Argentinian Angel Cabrera (64) two shots back on nine under alongside Percy, Canada's David Hearn (67) and Americans Matt Bettencour (67), George McNeill (64), Jon Curran (69), Dicky Pride (67), Jordan Spieth (66) and Morgan Hoffman (68).
Sweden's Henrik Stenson was the highest European challenger at the midway point on seven under after signing for a second-round 69.