Coach Vicente del Bosque made seven changes from the side that lost 2-0 to Chile, sealing an early exit for the holders.
Reina has replaced captain Iker Casillas in goal while Villa comes in for Diego Costa up front. Midfielder Andres Iniesta ha retained his place and will win his 100th cap.
Australia, who have also been eliminated, brought in 21-year-old striker Adam Taggart to replace the suspended Tim Cahill.
Midfielder Oliver Bozanic comes in for Mark Bresciano who had been struggling with injury.
(Writing by Keith Weir, 44 20 7542 8022)
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