West Ham United's European dream sadly ended at the first hurdle on a frustrating night in Italy, as Serie A table toppers Palermo secured a 3-0 victory in the UEFA Cup first round, second leg.
Despite a superb first-half performance, in which only misfortune and excellent goalkeeping prevented Hammers from levelling the tie, Alan Pardew's men were left to reflect on what might have been as a double strike from Simplicio and one from Di Michele saw the Sicilians progress to the group stages of the competition.
Both sides made wholesale changes following their 2-0 domestic defeats at the weekend. After seeing his side lose at Manchester City, Alan Pardew handed a debut to right-back Jonathan Spector, while James Collins, Lee Bowyer and strike-partners Carlton Cole and Carlos Tevez all started at the expense of Yossi Benayoun, Matthew Etherington and Bobby Zamora, plus injured duo Christian Dailly and Anton Ferdinand.
Francesco Guidolin was even more ruthless following his side's first Serie A reverse of the season at Empoli, as Alberto Fontana, Cristian Zaccardo, Eugenio Corini, Fabio Henrique Simplicio, David Di Michele and scorer of the first-leg winner, Andrea Caracciolo all returned to the home line-up.
With only skipper Corini missing from the fast and furious Upton Park showdown, that meant that no fewer than 10 of the players that had brought a slender, one-goal advantage home to southern Italy kicked off the second leg.
And amidst a hostile Sicilian atmosphere that saw Hammers's 2,000 loyal supporters making themselves heard on the Curva Sud, West Ham soon set about finding an away goal of their own in a frenetic opening that again saw the tackles flying in.
Only five minutes were on the clock when the teasing Tevez carved in from the left and unleashed an angled 12-yarder that was tipped over by Fontana for a corner and, shortly afterwards, Cole headed wide before the Palermo 'keeper stole the ball off Bowyer's toes.
Paul Konchesky then tried his luck from 20-yards and, with bright red, smoking flares blazing on the home terrace of the Curva Nord, Simplicio replied with a low shot from similar range that the alert Roy Carroll smothered.
Midway through the half, hesitation between Konchesky and Gabbidon almost proved costly, when Di Michele stole in, but the Northern Ireland 'keeper bravely smothered before blocking Aimo Diana's follow-up and then collapsing in need of treatment.
On 26 minutes, one thundering challenge too many finally saw Georgios Kasnaferis pluck a yellow card from his pocket, after Andrea Barzagli scythed through the back of the lively Cole.
And the former Chelsea striker was soon back in the thick of things when he sliced across goal, before Konchesky sent another 20-yard screamer inches wide of Fontana's left hand post.
The athletic Palermo 'keeper then palmed Harewood's acrobatic overhead kick skywards and, as West Ham turned up the heat, Bowyer's half-cleared corner fell to Cole, whose shot cannoned back off the body of the busy stopper who was then forced to tip over Collins' looping header.
But just as West Ham were getting themselves on top, a well-worked, 34th-minute free-kick by the pink-shirted Rosanero, saw Simplicio drill a low 18-yarder back through the pack and into the bottom left-hand corner of the diving Carroll's net, to double Palermo's aggregate lead, ahead of the break.
West Ham had kicked-off needing two goals for outright victory and, despite that Simplicio setback, they emerged for the second half in an identical position.
That said, they had Carroll to thank for keeping them in the tie when he beat out Mark Bresciano's early shot and then foiled Zaccardo's far post header.
On the hour, the flying Cole launched himself at Spector's teasing cross but in sending his header onto Fontana's right-hand post he fell awkwardly and was stretchered away.
The unfortunate striker's replacement, Bobby Zamora, had barely joined the action, though, before Hammers UEFA hopes were shattered by that man Simplicio, who coolly lobbed the ball over the helplessly exposed Carroll, after Di Michele robbed the hesitant Gabbidon to send the Brazilian bounding clear.
And on 67 minutes, the suspiciously offside looking goal-maker turned goal-taker when Di Michele raced behind the pushed-up Hammers defence and slotted between the appealing Hammers' 'keeper and his left-hand upright.
As the Italians amongst the 19,284 crowd went wild, the equally furious Carroll added to Greek referee workload, when he joined Barzagli, Corini, Zaccardo, Cassani and Cole on the yellow card list.
Pards immediately responded by replacing Javier Mascherano and Marlon Harewood with Teddy Sheringham and Yossi Benayoun but, by then, the four-goal aggregate margin had turned the Euro dream into a nightmare.