"We had people scoring from all different positions," said Granger, who also grabbed six rebounds. "It was just a total effort, and that's what we're going to need."
Allen Iverson finished with 20 points on 8-of-22 shooting from the field for the 76ers (3-1), who trailed by at least 10 points the entire second half. Kyle Korver and Willie Green each scored 14.
For the second time in its past three games, Philadelphia was outrebounded by 20 or more. The Pacers held a 52-32 rebounding edge on Tuesday.
"You can't teach rebounding," Iverson said. "We're not going to be able to win basketball games if we don't rebound the ball."
The Pacers used their defense and rebounding to take control in the second quarter.
After falling behind by three at the end of the first period, Indiana used a 10-2 run to jump ahead. The Pacers extended their lead to 51-36 at the half by scoring 11 of the final 13 points before the break.
Indiana started the second half by hitting three 3-pointers, two by Harrington, to push its lead to 60-39. The 76ers cut the deficit to 64-47 with 5:10 left in the third quarter, but O'Neal's layup halted Philadelphia's momentum.
The 76ers began the fourth quarter with five straight points, which included a powerful one-handed dunk by Steven Hunter over Pacers center Jeff Foster, but Foster came right back and stopped the run with a basket of his own.
"The defensive energy we had tonight was the best we've had all year," Pacers coach Rick Carlisle said. "It shows real unity when you can get 12 guys to commit to the defensive end."
The 76ers struggled to get scoring from anyone besides Iverson through the first three quarters.
"We just never got another guy to score," Philadelphia coach Maurice Cheeks said.
O'Neal said he slightly sprained his left ankle during the third quarter after coming down awkwardly on a shot attempt. He said he will play in Wednesday's game at Washington. ... Iverson's streak of six straight games with 30 or more points dating to last season ended. ... Pacers guard Sarunas Jasikevicius missed Tuesday's game with a sore back. He's listed as day-to-day. ... Carlisle was whistled for his first technical foul this season after arguing a no-call early in the third quarter. ... Philadelphia forward Alan Henderson, a former Indiana University star, received a nice ovation from the crowd at Conseco Fieldhouse when he entered the game late in the second quarter.