She missed last year's tournament while pregnant.
And given Raonic was the last man to beat Federer at Wimbledon, that might provide hope to those players.
"I think I can be very happy today", said Federer, who will next face France's Adrian Mannarino.
The 38-year-old American, last year's runner-up, was the oldest women's singles entrant in 2018.
She rallied to level the third-round match before Rodina sealed a maiden place in the last 16 of a major.
Defending champion Garbine Muguruza, second seed Caroline Wozniacki and two-time champion Petra Kvitova are amongst those that have suffered early exits and as a result, the women's draw is as open as it's been in more than half a century.
Pella, a clay-court specialist who until Thursday had never reached the third round of a Grand Slam and until this week had yet to win a match here, claimed the biggest scalp of the day as the 28 year-old overturned a two-set deficit in breath-taking fashion, finally converting a fourth match point in the fifth.
Del Potro faces Benoit Paire in the third round after the Frenchman upset 26th-seeded Canadian Denis Shapovalov.
The South African eighth seed reached the third round when he completed a four-set victory over Italy's Andreas Seppi on Thursday.
The world number 64 has had to fight back from two sets to love down in his first two matches to beat Leonardo Mayer and 39-year-old Ivo Karlovic.
The seven-time champion came from a break down in the first set to get past Kristina Mladenovic 7-5, 7-6 (2).
Nick Kyrgios, the 15th seed, also advanced in straight sets, beating Dutchman Robin Haase 6-3 6-4 7-5 to book a date with Kei Nishikori, who ousted Kyrgios's fellow Australian Bernard Tomic 2-6 6-3 7-6 (9-7) 7-5.
"I worked really, really hard (to get back playing) and it's been a long, arduous road but I always expected to come out and do the best I can do".