I think the next season will see the end of Rita's children as they will likely be taken in by her ex-husband's parents who conveniently took them on a trip in the last episode of Season 4. Or the likely situation is that Rita's mother will swoop down from Michigan and try to scoop up all three kids including Harrison. She's already been made to believe her daughter married a recovering drug addict. Now Rita's been found murdered in Dexter's own home. A woman of her personality will not remain silent. This is just the fuel she needs embark on a crusade against our Hero, Dexter.
I also believe that the coincidences have been piling up for Dexter and that Quinn may begin to suffer from the same obsession Doakes had in Seasons 1 & 2. Or, he may attempt to reconcile with Dexter due to the fact they have something in common. They both lost their excess baggage in a violent manner.
If Dexter isn't suspected, at least momentarily, for Rita's death I'll be surprised and slightly disappointed for it goes against reality.
I think we'll find more camera time for Angel Batista and if we don't we should. He's yet to fulfill his potential on the show and a lot of people can relate to the goodness of his character.
Hopefully we'll see a return, at least in part, of Harry's influence in the past tense--memory fashion rather than this present day, hallucination/angel-on-the-shoulder he has been in the last 2 seasons.

Going back to what I said about Harry, I really hope Julie Benz AKA Rita doesn't become another apparition in Dexter's daydreams. Pretty soon that could get out of control and it will be like the end scene of Return of the Jedi with Obi-Wan, Yoda, and Luke's father all hanging out in the glow of their own auras. It would be nice to see a little more involvement with Vince Masuka. Maybe he has doubts about his colleague this season, or in contrast, rises up to clear Dexter's name. Assuming they don't skip ahead too far in the future like they did between Seasons 3 and 4, all these ideas are plausible. Say NO to little Harry with acne.
If the subplot of Quinn & Debra's growing appreciation turns to romance it could lead the show down a regrettable path. Besides, that will only leave LaGuerta as the last thing on two legs Debra hasn't had sex with or cried in front of.

To be quite honest, the "ultimate SK" plot has run its course and Dexter will likely not be too interested in a friend or mentor for some time. He'll have to play pretty close to the chest with Rita's murder occurring in their home.
Can't blame the guy for not wanting friends. When he does extend himself he gets Jimmy Smits!! That's like going to Italy and ordering Little Caesars pizza.
I predict a shift in emphasis away from Dexter's victims' crimes. It will be more about the kill and less about glorifying their actions. Otherwise, since Trinity, they'll do that idea to death, all puns intended.
Everyone who says this Rita incident is going to be a real problem for Dexter is probably Spot-On. I said it myself. And Quinn could go two ways. He could comfort Dexter because he lost his girl in a violent manner too. Or he could become another Doakes and obsess over taking him down. I DO see a relationship forming between Quinn and Debra. He may use that for leverage against Dexter. I think what we forget is we don't know what side Quinn is ever on. There's more about him we still don't know. He may have a few kills under his belt, too. If he does, he'll reveal it this season and be dispatched shortly thereafter.
What's great about the show is the writers know how to inventory a lot of subplots and later take them off the shelf when their time comes to reach their full potential.

I'd love to see LaGuerta get shot in the line of duty this season (she was dead by the end of the first book anyway, and Batista wasn't a cop. He was a medical examiner) Sorry Angel, but you're too great of a character to have every story revolve around your unholy bond with Satan.

In an effort not to see a rehashing of something already done, I'd say avoid taking too many elements from existing characters and movies. It has to remain in most part, pure to the show Dexter. Otherwise it's Hack work that cheapens the experience. What would be nice is a return to references and vague similarities. That way if you know the story of the real serial killer, you'll feel intelligent for having noticed the resemblance.
H. H Holmes would be too much. Bela Kiss may be easier to pull off. Fritz Haarmann, Peter Kurten, Albert Fish, Harold Shipman, Fred & Rosemary West--These would all be solid choices for victims of Dexter's.
Here's something else we haven't seen yet. Dexter goes after someone he finds out about without the use of police resources, but they get arrested before he can issue his ultimate justice. We haven't seen a Gacey-esque character as of yet. I don't think Dexter's first kill in Season 1 Episode 1 qualifies for that even though the guy killed young boys. I like how the nurse who was over medicating Harry was modeled after Jane Toppan. Granted, sometimes they merge details of more than one SK into one personification. But there is still much more work to be done. The skinner was somewhat like BTK, and the physical appearance of Bryan Moser was modeled after The Night Stalker, Richard Ramirez.

The more quick references the more enhanced each part becomes. When Dexter was ordering his tranquilizer he used the name, Patrick Bateman. That was Christian Bale's character in American Psycho. It was a quick, subtle reference that only someone truly paying attention would appreciate. And that is what we need more of. It gives the real fans a reward for their loyalty. These are the little gems a smart writing staff leaves for their fans to discover.

What I was saying about Dexter not using police sources to find a criminal would be great if he happened to witness someone in a suspicious act first hand. He may follow the person and discover a dark secret. Maybe it will be a stranger, or perhaps a person he knows well. Maybe Quinn will be at the docks doing business with bad people or something. It's just a thought, nothing more.

What they did with Season 4 raised the stakes and reinvented the game for the writers. They have to outwit themselves this season or it will pale in comparison. No cheap parlor tricks will do. There can't be any weaknesses. I wouldn't be surprised if an episode or two are devoted almost completely to developing the stories around Dexter that he has no direct involvement in. I think we'll find ourselves watching other people rise and fall in an effort to complete what the writers have started. Dexter would always be #1, after all he's first-person omniscient when he narrates. We need more Dexter. Last season's necessary evil was getting the subplots rolling at the expense of camera time for Dexter. Hopefully they will merge the stories before too long so our main character is involved, even when they're working something through to its end.
If you make more than one character interesting it is good for dynamics. We already like the lesser played pawns (Batista, Masuka, etc.), so why not let them move about the board a little more this season? Strategically, of course.
From the perspective of appeal to audiences, there has to be something for everyone if you want to expand your audience. There are ways of doing this without cheating your die-hard fans of the substance they deserve. In fact, when done right, it benefits everyone. But they have to do this better than last season. They have to make the subplots interesting and involve Dexter more.

My Advice to the Writers:
The SMART BETS
1.) Give Masuka a bigger role. He showed an admirable loyalty to DEXTER at Thanksgiving when he saw Rita and the neighbor kissing. Let's develop that into a closer relationship with Dexter. If Dexter's to have any friend at this point, better it be the only guy the series shows as being the likely candidate to investigate one of his own crime scenes.
2.) I'll say it again: Kill LaGuerta. Let her get shot for being the crappy detective she is, or better yet let her negligence lead to the death of an officer under her command. That way we'll see her ignorance, her tragic flaw, be the thing that brings her down. Maybe she should get put in jail for it.
3.) Crap or get off the pot (and the show) Quinn. Reveal the real Quinn to us. Is his past shady? Or is he the tragically misunderstood? Whatever the case, it would be nice to send him out in combination with my suggestion above. Maybe LaGuerta will be responsible for putting him in harms way. Likely, she'd put a no-name character in the grave instead, though.
4.) Batista gets LaGuerta's job. That would be great. The only fear I have with shifting people around within the force is having Debra get yet another promotion. She has moved up too fast already. It will become almost cliche if she earns a higher rank every season as standard practice. That would be less than realistic for someone without political ties.
5.) Addition of new characters in the police divisions. More dirty cops within the force to take the attention off Dexter. Preoccupation of the force is key to lightening Dexter's heavy load.
6.) Dexter better be a suspect in Rita's Death. It's standard to accuse the spouse. If they spend a half, or four episodes on this it doesn't matter. It just needs to be an option the police explore. Let's be realistic.
7.) Rita's kids should be adopted by their grandparents who were conveniently taking them on a trip in the last episode. I'll be sad to see Cody go, but I'll get over it because it means the bitchy daughter doesn't make this into an "I hate my stepfather" show. They've run their course. They came with Rita and they should leave with her.
8.) Harrison gets a nanny. Maybe the first one has a dark past. Family is again in jeopardy. Or you may see Debra getting more involved with Harrison and through that an evolution occurring in her character.
9.) Dexter stays single! For at least the majority of the season Dexter needs to focus on damage control. Maybe a new acquaintance can be a subplot later developed in a future season.