Sam (Jared Padalecki) and Dean (Jensen Ackles) Winchester didn't exactly have a stable childhood in the Supernatural series. Their mother was killed by a demon when Sam was a baby, and their father became obsessed with finding and killing the demon who did it, often leaving the kids to fend for themselves in roadside motels. The brothers found a family among those they met while hunting. They had a lot of people watching their backs, and they gave the same in return.
The brothers may have had absent parents (their mother continued to be absent even after her resurrection), but they didn't lack family. From Jody (Kim Rhodes) stepping up as a mother figure, to Charlie (Felicia Day) becoming the "little sister Dean never wanted," there was always someone offering support.
Bobby Singer
Bobby Singer (Jim Beaver) was a hunter and close friend of John Winchester's (Jeffrey Dean Morgan). It was Bobby who originally told the boys that "family don't end with blood." Acting as a father figure to Sam and Dean when their biological father was away (which was often), he made sure they were taken care of.
Bobby even came back as a ghost to help the boys with cases, proving that they were more important to him than Heaven. Dean eventually burned Bobby's flask at Bobby's request, releasing his spirit to Heaven. However, in later seasons, the boys met Bobby from an alternate universe, and he returned to the bunker with them. He didn't know them well, but he did know Mary Winchester (Samantha Smith) in his world, and again stepped up as a father figure.
Rowena Macleod
Rowena (Ruth Connell) was Crowley's (Mark Sheppard) mother and a powerful witch. She originally played a villain, but found herself reforming and working alongside the Winchesters. She died three times helping them: twice at the hands of Lucifer (Mark Pellegrino) to keep her from locking him in the cage, and finally, when she sacrificed herself to help the Winchesters save the world in the final season.
When Lucifer killed Rowena, she'd used a resurrection spell that saved her both times. The second time he killed her, it took her some time to fully recover due to the extent of her injuries. When the Winchester's battled God (Rob Benedict) in season 15, Rowena made the ultimate sacrifice. She had become a much-loved part of the family business by the end of the series, and her death was devastating for the brothers.
Garth Fitzgerald IV
Garth (DJ Qualls) didn't hunt with the Winchesters often, preferring to hunt solo. He was bitten by a werewolf on a hunt, and after being turned into one himself, he retired from hunting, married another werewolf, and joined her pack. The couple had twins Sam and Castiel, and Garth was content with a "normal" life. When the Winchesters were in a life-or-death situation at a monster fight club in season 15 after God turned the brothers into normal people, Garth saved the day.
It's hard not to love Garth. He wasn't always the greatest hunter, but his heart and determination more than made up for it. Even though he retired from hunting, he still helped his fellow hunters by assuming Bobby's old job of taking calls and researching monsters. But, his true shining moment was in the last season when he dropped everything to save the Winchesters from the fight club, and was finally the hero.
Jody Mills
Jody was sheriff of Sioux Falls and met the Winchesters while they were there investigating the rising dead, including Jody's young son. Sam was forced to kill the boy after he murdered Jody's husband. With no family left, Jody became a hunter and helped the brothers with cases whenever they needed it, and they did the same for her. By the end of the series, she would have given her life to protect them.
If Bobby was the father figure in the series, then Jody was the mother figure. She was always there to support her adopted daughters, as well as the Winchesters. After meeting Mary, the two talked about Sam and Dean, and it was obvious Jody considered them her boys, too. She made an appearance in every season since joining the series, and was nearly given a spinoff called Wayward Sisters with her adopted daughters.
Charlie Bradbury
Charlie was introduced in season 7 when she helped the boys defeat the Leviathan. A self-proclaimed nerd, Charlie was a genius hacker and loved everything pop culture. One of her strongest qualities was that she wasn't afraid to be herself. She and the Winchesters became close, and her hacking skills often came in handy on cases. It was even revealed in season 15 that she had set them up with a credit card for life.
Even though their first meeting was less than ideal, and Charlie joked at the end of the episode that she hoped to never see the brothers again just before boarding a bus, she did end up becoming an important part of the family business. Over time, the three developed a close relationship, and Charlie became "the little sister Dean never wanted." Because of that, her brutal murder while working on a case with the Winchesters was something Dean would never forgive himself for.
Crowley
Crowley started on the series as a crossroads demon, and originally worked for Lilith until her death. He eventually promoted himself to King of Hell after Lucifer was locked back in the cage, and allied himself with the Winchesters off and on throughout the series. When Dean became a demon after accepting the Mark of Cain, Crowley took him under his wing, and the two became best friends. Although Dean was eventually cured, their bond remained, prompting Crowley to help the Winchesters more than he probably cared to admit.
Crowley's humanity started to show when Sam "cured" him with purified blood as one of the Trials of God. After that, Crowley played both antagonist and anti-hero, usually helping when it benefited him. Still, his conscience often got in the way of his decisions, and he usually ended up helping the Winchesters. He even sacrificed himself to defeat Lucifer and, just like his mother, Rowena, he gave one final "Goodbye, boys" before plunging an angel blade into his stomach for the good of mankind.
Castiel, Angel of the Lord
Castiel (Misha Collins) joined the series in season 4 when he pulled Dean from Hell. In the beginning, Castiel was disconnected from humanity and had no problem killing innocent people if necessary. His devotion eventually shifted from God to the Winchesters, and he began to develop more human traits, including compassion -- something angels lacked in Supernatural. As Castiel realized that God was not good, he rebelled and the Winchesters became like family to him.
The brothers had a close friendship with Cas, but he and Dean shared a closer bond than Cas did with Sam. When Dean blamed Cas for his mother's death, it ripped Castiel apart. However, as family does, Dean and Cas eventually reconciled. At the end of season 15, Cas sacrificed himself to save Dean in an emotional goodbye that ended with, "I love you, Dean," leaving 'Destiel' fans reeling over the intention of those words.
Jack Kline
Jack (Alexander Calvert) is the son of Kelly Kline (Courtney Ford) and Lucifer, making him a powerful Nephilim. After Kelly died during childbirth, Sam, Dean, and Cas took care of a swiftly growing Jack, and ensured he didn't inadvertently hurt or kill anyone. Jack's mother had a kind soul, and much of that passed on to Jack; despite his paternal lineage, he was kind-hearted. After he took God's powers and became the new God, Jack transformed Heaven into the happy place it was meant to be.
Jack was like a son to Sam, Dean and Cas. Even when Bobby told Dean about the changes Jack made in Heaven, he started with, "That kid of yours...." Despite Sam and Dean's unstable upbringing, they were good parents. They and Cas taught Jack right from wrong, and how to use his powers for good rather than evil. In turn, Jack made sure his dads got "the Heaven they deserved."