Ola Toivonen nearly gave the hosts the early goal they needed but was denied by a fine save by Diego Alves, before an even better stop from Przemyslaw Tyton prevented Valencia going in ahead at the break as he tipped Jordi Alba's attempted lob wide of the post.
The visitors did go in front two minutes after half-time as Sofiane Feghouli's shot deflected in off the head of Adil Rami, but Toivonen gave PSV hope when he coolly slotted past Alves from close range 15 minutes later.
The Brazilian goalkeeper denied PSV victory on the night with a stunning save from Kevin Strootman before Valencia had to see out six minutes of stoppage time with 10 men as Rami was shown a straight red card following a collision with Toivonen.
Trailing 4-2 from the first leg, PSV knew they had to push forward but after a positive start it was Valencia who had the better chances in the first period.
Jonas Goncalves' fierce drive was beaten away by Tyton before the Brazilian came even closer minutes later with a shot which crept just over the bar.
Toivonen then had the hosts' best chance of the opening period but Alves got down well to his right to parry the Swede's powerful header.
Both sides could then have scored in a frantic end to the half. Alba's deft lob looked destined for the net only for Tyton to somehow get a hand to the ball to divert it wide, and from the resulting corner Aritz Aduriz headed over from only a couple of yards.
At the other end Georgino Wijnaldum should have done better when presented with the ball inside the area, but Rami recovered well to block his shot.
The deadlock was broken after the break in somewhat fortunate circumstances as Feghouli's scuffed shot from outside the area struck Rami and wrong-footed Tyton to dribble into the net.
PSV continued to press though and were deservedly level on the night when Toivonen chested down a loose ball in the box and sidefooted past Alves at his near post.
Alves came to Valencia's rescue again to prevent a grandstand finish as he brilliantly turned away Strootman's rasping drive, while the game ended in confusion when Scottish referee Willie Collum sent off Rami for an off-the-ball incident with Toivonen and initially awarded the Dutch side a penalty before reversing the latter decision and giving a free-kick to Valencia.