Both remounted, with GC outsider Kelderman being chaperoned back to the strung-out bunch by his team-mates, though Manxman Christian took longer to get going again.
Rubio and Rossetto did not work well together, attacking each other as the pressure from behind began to tell, and it was gruppo compacto with 8km still to race on the technical finale.
Just short of the three-kilometre-to-go kite, Domenico Pozzovivo (Ag2r-La Mondiale) and Daniel Moreno (Movistar) hit the deck in a crash towards the back of the bunch – the former’s GC bid taking a big hit as a result.
Passing under the flamme rouge, QuickStep Floors were on the front, but had Blythe riding their wheels as they headed onto the highly technical final kilometre.
Lobato opened up his sprint first, with Blythe boxed in further back, but Trentin had open road before him to accelerate out of Lobato’s wheel and take the stage win.
Blythe finished 15th in the end, two places in front of Froome as the Team Sky man retained his red jersey.
Pozzovivo’s crash, meanwhile, means Simon Yates (Orica-Scott) moves into the top ten overall, with brother Adam staying in eighth.
Vuelta a Espana 2017: stage four – result
1) Matteo Trentin (ITA) – QuickStep Floors – 4.43.57hrs
2) Juan Jose Lobato (ESP) – LottoNL-Jumbo – ST
3) Tom van Asbroeck (BEL) – Cannondale-Drapac
4) Edward Theuns (BEL) – Trek-Segafredo
5) Jens Debusschere (BEL) – Lotto-Soudal
6) Sacha Modolo (ITA) – UAE Team Emirates
7) Lorrenzo Manzin (FRA) – FDJ
8) Soren Kraigh Andersen (DEN) – Team Sunweb
9) Youcef Reguigui (ALG) – Dimension Data
10) Jetse Bol (NED) – Manzana Postobon
1) Chris Froome (GBR) – Team Sky – 13.37.41hrs
2) David de la Cruz (ESP) – QuickStep Floors +2″
3) Nicolas Roche (IRL) – BMC Racing – ST
4) Tejay van Garderen (USA) – BMC Racing
5) Vincenzo Nibali (ITA) – Bahrain-Merida +10″
6) Johan Esteban Chaves (COL) – Orica-Scott +11″
7) Fabio Aru (ITA) – Astana +38″
8) Adam Yates (GBR) – Orica-Scott +39″
9) Romain Bardet (FRA) – Ag2r-La Mondiale +48″
10) Simon Yates (GBR) – Orica-Scott – ST