Rotherham Chief Executive Jim Kilfoyle stressed the importance of a home win earlier in the week and the Titans got off to a fantastic start when No.8 Geraint Lewis crossed over for a try in the first minute. Titans fly-half Jason Strange extended the lead with the conversion.
It did not take long for Harlequins to take charge, however, starting with a penalty struck by Irish fly-half Paul Burke. Ugo Monye, fresh off his double against champions Wasps last week, went over for his first try of the game in the 15th minute.
Burke and Monye were back in the action not long after when Quins secured a turnover in midfield ending in Burke releasing to Monye on the wing, who completed the move with a galloping run down the field to cross for his second.
The visitors were well in control before the break and the Titans could only look on as former Leeds winger George Harder darted around Jason Keyter for Quins' third try of the game. Burke made no mistake with the conversion and stretched the lead to 20-7.
The Titans' misery was not over yet, however, as Harder broke down the touchline and offloaded to Samoan Ace Tiatia for the fourth try and the bonus point.
The home side tried to fight back after the break and would have taken heart from captain Chris Johnson's try, but with two more Burke penalties Quins had safely wrapped the game up and began to ring the changes.
Monye wrapped things up with his third try as Harlequins continued their impressive start to the season.
For Rotherham:Tries: Lewis, JohnsonCons: StrangePen: Strange
For Harlequins:Tries: Monye 3, Harder, TiatiaCons: Burke 2, Dunne Pens: Burke 3, Dunne