Harang (4-7) limited his former team to a pair of runs and six hits, including Joey Votto's 15th homer. Oliver Perez struck out the side in the ninth for his second save.
Franklin hit a two-run homer off Mike Leake (7-4), who had his start pushed back one day by a rainout. Saunders had a solo homer and a sacrifice fly off Leake, who lasted five innings.
The Mariners are making their second visit to Cincinnati and their first to Great American Ball Park, which opened in 2003. In their other trip, they swept a three-game series at Cinergy Field in 2002. The Mariners are 9-1 all-time against the Reds.
Seattle and Cincinnati will always have one notable baseball connection: Ken Griffey Jr., who grew up in Cincinnati, developed into one of the majors' best with Seattle, and returned to his hometown in a trade before the 2000 season. Griffey finished his career in 2010, when he retired from the Mariners.
Harang pitched for the Reds from 2003-10, starting five season openers. He holds the record for most career strikeouts at Great American Ball Park with 598, including his four on Friday night.
It was the first time the 35-year-old pitcher had pitched at Great American since he left the Reds as a free agent.
Leake originally was scheduled to pitch on Thursday against San Francisco, but got pushed back a day because of a rainout. Leake had allowed only nine earned runs in his last nine starts, going 5-1 with a 1.31 ERA.
That stretch of fine pitching ended quickly.
Brad Miller, batting leadoff for the first time, hit Leake's third pitch for a triple to right-center. Franklin homered on the next pitch.
Saunders led off the second inning with his fifth homer. He hit a sacrifice fly in the fourth for a 4-0 lead, the most runs Leake had allowed in a game since May 8.
Miller also tripled down the right-field line in the fifth but was stranded at third. He's the first Mariner to have two triples in one game since Carlos Guillen in 2003 and the 13th overall, according to STATS LLC.
Seattle slugger Raul Ibanez extended his hitting streak to 11 games with a single.
NOTES: The Reds honored Homer Bailey on the field before the game for his second career no-hitter on Tuesday night against San Francisco. Jim Maloney, who also threw two no-hitters for the Reds, joined in the festivities and threw a ceremonial pitch to batterymate Johnny Edwards. ... Franklin's homer gave Seattle 20 in the first inning this season, most in the majors. ... Saunders had been out of the lineup the last six games with a finger injury. ... Mariners OF Michael Morse, on the 15-day DL since June 22 with a strained right thigh, plans to run the bases on Saturday to test the leg. He's close to starting a rehab assignment. ... The Reds wore white Fourth of July caps that were made for Thursday's game.