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Over the second half of last season, “Grey’s Anatomy” went from being the TV pal with whom every get-together feels like a giddy first date, to the grating houseguest who constantly gets on your nerves.


You know the storyline: Off screen, cast members squabbled over Isaiah Washington’s nasty homophobic slur. On screen, a dark cloud hung over Seattle Grace as death, destruction and personal devastation reigned. And oh, those creative missteps: George (T.R. Knight) and Izzy (Katherine Heigl) making booty calls? Ugh.


By the time the season of discontent was over, two key members of the cast were gone - Washington getting the heave-ho and Kate Walsh getting her own spin-off show in “Private Practice” (9 p.m. Wednesday, ABC). Gone, too, was much of the good will the show had built up with fans and critics.


As “Grey’s” returns for its fourth season (9 p.m. Thursday, ABC), its vital signs are flagging and one has to wonder: Can this show get back to being the frothy, intoxicating guilty pleasure it once was? Fortunately, creator Shonda Rhimes is saying all the right things: It’s time to lighten up, sex it up and have a ball.


“I came back to this season sort of mandating that we have a lot of fun,” she told TV writers this summer. “I felt like Season 3 is a darker season. It just is. I mean, Meredith’s (Ellen Pompeo) mother dies. George’s father dies. Meredith’s stepmother dies. It was a bloodbath. But I want to get back to us enjoying it and having fun.”


Still, Rhimes by no means cops to creative mismanagement. While she admits the behind-the-scenes rancor of last season was “difficult,” she stands by the direction of the show’s storytelling. (“It felt like the journey these characters needed to take.”). And she even defends the hotly debated “Gizzie” plotline.


“I understand it,” she says of negative fan reaction to the unexpected coupling. “I think, when Meredith and Cristina (Sandra Oh) and Alex (Justin Chambers) find out, they are going to have some pretty vitriolic reactions as well. I think that’s part of what makes it interesting. The characters are flawed. The characters are really human.


And I’m not necessarily saying that George and Izzie are the love story of the century. People make mistakes. And perhaps this is a mistake. Perhaps it isn’t. But I think it’s an interesting thing to explore when you decide that your best friend is your soul mate.”


She has a point. That “Grey’s” has adventurously embraced personal flaws and messy “mistakes,” is one of the traits that makes it so intriguing. How many shows, after all, have a put-upon title character who inspires so much love-her, hate-her buzz? But it’s a tough act to consistently pull off.


If plot developments become too outrageous and/or annoying, it becomes much easier for us not to care. How much longer, for example, will fans put up with the George-and-Lizzie melodrama? And more importantly, how many more Meredith-Derek (Patrick Dempsey) breakups can we take?


The cast departures also are cause for concern. Washington’s complex genius Dr. Burke was a fascinating character and proved to be the perfect yin to Ms. Yang. As for Walsh’s Addison, she arrived on the scene as a bit player who you wanted to detest. But she deepened into a strong, classy, engaging woman who provided a welcome respite from the intern drama queens. Both were key components.


As “ER” repeatedly proved over the early part of its run, a medical show can withstand significant departures and remain involving if it makes the right casting choices. Maybe Chyler Leigh, who joins the Seattle Grace gang as Meredith’s half-sister, Lexie, will make us forget Burke and/or Addison. Maybe not.


Either way, it will be interesting to see if “Grey’s” can recapture the magic. When the show is at its best, it delicately blends sober drama and real emotion with unpredictable twists and breezy humor (with breezy being an operative word). It’s a potent brew that keeps us captivated and gets us talking.


“I take really seriously what the fans say. I kind of love that people feel this strongly about the show,” Rhimes says. “What that means to me is that they are watching it and that they care about it and that they feel as emotionally connected to the characters as I do.”


___


WEDNESDAY SHOWDOWN: Oh how perfect it is that the exiled Washington winds up in a show (“Bionic Woman,” 9 p.m. Wednesday, NBC) pitted directly against Rhimes’ new baby, “Private Practice.”


Washington isn’t in Wednesday’s pilot - he appears in five upcoming episodes - but the show gets off to a strong start without him as British import Michelle Ryan makes a strong first impression as the 21st century Jaime Sommers.


Fans of Lindsay Wagner’s 1970s cult hit won’t find much carryover in this reinvention, which is darker, sleeker, sexier and more technically turbo-charged than the original. So don’t expect any appearances by Big Foot any time soon..


What you can expect is a bold performance by Katee Sackhoff (“Battlestar Galactica”), who plays a bionic babe gone bad. In the opener, she locks up in a hellacious rooftop throw-down with Ryan that will have sci-fi geeks gasping in delight.


As for “Private Practice,” it offers a very different kind of reinvention: Walsh’s Addison heads to L.A. to begin life anew at a wellness clinic and leave her horrible McNightmare far behind. The good news is that Wednesday’s pilot improves considerably on last May’s preview episode. The bad news is that it still feels somewhat “Ally McBeal”-ish and it also remains to be seen if this cast of all-stars (including Taye Diggs, Tim Daly and Amy Brenneman) will truly gel into an appealing ensemble.


Speaking of the cast, Audra McDonald replaces Merrin Dungey as Addison’s best friend, Naomi. And only one “Grey’s” character appears in this week’s episode - the Seattle Grace chief (James Pickens Jr.), who reluctantly accepts Addison’s resignation and watches her bolt Seattle for good.

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