Why is this on the Versus Thread Board? Put it in Fun and Games.
Doflamingo wins because unlike before, he wont be rendered weakened by a mortal wound that required immediate attention just to prevent himself from dying on the spot.
Luffy would still be rendered incapacitated upon using Gear 4th excessively, which he would need to in order to actually defeat Doflamingo. Anything less than King Kong Gun couldn't KO Doflamingo, even while in a weakened state.
Even in-plot, Doflamingo was chained up in sea-stone and taken away moments after he was struck by KKG, and Luffy was unconscious for more than 2 days. Who is to say that Doflamingo wasn't the first one to wake up? He was seen later having a conversation with Tsuru in pretty good health considering what he just dealt with.
In fact, since this is basically just a re-hash of the Dressrosa arc excluding outside help, the fight would play out almost identically to their first round, with Doflamingo using the Black Knight to blind-side Luffy, and proceeding to capitalize and harass Luffy with his 2-on-1 advantage, not to mention his superior strength and durability.
Luffy would be forced to go into Gear 4th while roughed up and Doflamingo would be in perfect condition, and while Gear 4th would turn the tables rather quickly, Doflamingo still has his awakening, and he'd be able to use haki on it this time since he isn't forced to focus on recovering his body.
He'd be able to hold off Gear 4th much better this time, so either Luffy uses King Kong Gun and manages to land a blow on Doflamingo, which would probably not KO him at this point, and Luffy would be unable to even move for 10 minutes while no one would be there to help him. Doflamingo would have plenty of time to get up, even when critically injured because of his powers and endurance, and just de-cap Luffy.
Whole-Cake Luffy is a totally different matter <_<