Because You're Still....Breathing

I learned from here that Amy and Rory will be leaving as companions sometimes during season seven. Since the first episode I ever watched was "The Eleventh Hour," I have a special affection for Amy as my companion, just as Eleven is my Doctor. Rory is also one of my favorite companions, the amazing Lone Centurion.
I really enjoy the Two Who Waited, and they have some great banter with the Doctor, such as the conversation in "The Doctor's Wife

Rory: He'll be fine. He's a Time Lord.
Amy: It's just what they're called, it doesn't mean he actually knows what he's doing.

As for the Doctor...he seems much more upbeat than Ten, but so many moments suggest he thinks otherwise. After all, the first major thing he does is leave his future companion for twelve years. Some episodes in season five hinted at this, but season six blew it wide open.

Doctor to Dream Lord: I know who you are. There's only one man in the universe who hates me that much.
After the revealation that the Dream Lord was physic pollen feeding on him
Amy:
But those things he said about you. You don't think any of that's true?
--Amy's Choice

While Rory's being erased from time

Amy: Tell me it's going to be okay. Make it okay.
The Doctor: It's going to be hard but you can do it. Tell me about Rory, huh? Fantastic Rory. Funny Rory. Gorgeous Rory. Amy, listen to me: do exactly as I say. Amy please, keep concentrating you can do this.
Amy: I can't.
The Doctor: You can. You can do it. I can't help you unless you do. We can still save his memory.
--Cold Blood

The Doctor is poisoned and summons the voice interface:

The Doctor Hologram: Voice interface enabled.
The Doctor: Oh no no no. Give me someone I like
(Rose, Martha, Donna, and Amy are rejected as guilt, also guilt, and more guilt)
Amelia Hologram: Voice interface enabled.
The Doctor: Oh. Amelia Pond. Before I got it all wrong. My sweet little Amelia.

--Let's Kill Hitler

To Rita
Rita: Why is it up to you to save us? That's quite a God Complex you have there.

The Doctor: I brought them here. They say it was their choice, but offer a child a suitcase full of sweets and they'll take it. Offer someone all of time and space and they'll take that too. Which is why you shouldn't. Which is why grown-ups were invented.
The God Complex

As the Minotaur approaches

The Doctor: I can't save you from it. There's nothing I can do to stop this.
Amy: What?
The Doctor: I stole your childhood and now I've led you by the hand to your death. But the worst thing is I knew. I knew this would happen. This is what always happens. Forget your faith in me. I took you with me because I was vain. Because I wanted to be adored. Look at you, glorious Pond. The Girl Who Waited for me. I'm not a hero. I really am just a madman in a box. And it's time we say each other as we really are. Amy Williams. It's time to stop waiting.
--The God Complex

Amy: So. You're leaving, aren't you?
The Doctor: You haven't seen the last of me. Bad penny is my middle name. Seriously, the looks I get when I fill in a form.
Amy: Why now?
The Doctor: Because you're still breathing(...)
Amy: Even so, it can't happen like this. After everything we've been through, Doctor. Everything. You can't just drop me off at my house and say goodbye like we shared a cab.
The Doctor: What's the alternative? Me standing over your grave? Over your broken body. Over Rory's body.
--The God Complex

From what I can see, the Doctor is haunted by a sense of failure regarding Amy and Rory--even saying he "got it all wrong" with her. And especially when you add the Melody/River factor into the whole story...sometimes I wonder if he can look at her without his heart breaking because of everything that happened to her since she was Amelia, since the fish fingers and custard (I find the two uses of 'Fish fingers and custard' in season six significant--once from Amy to the Doctor to convince him to trust her, and once from the Amelia hologram, which convinced the Doctor to keep going.)
As far as story lines go, I think the time has come for the Ponds to leave the TARDIS. As much as I love them, I think they need an ordinary life, with time for Amy to mourn for Melody, the daughter she will never raise, even while she has River. Not that I want them to die, but in one of my stories from Amy's perspective, I wrote

Time travel will be the death of us. I cannot see Rory and I growing old anymore. Even the surreal Leadsworth of the Dream Lord is too mundane now. Rory's ponytail—if that was our adventure, a ponytail and a planet belly-was it foreshadowing that we can't leave the TARDIS and pick up where we left off?

As for replacement companions, my dream would be having Luke Smith from the Sarah Jane Adventures join the TARDIS. Maybe others of the gang, but definately Luke. The resulting adorkableness would reduce me to absolute babbling. Or if not Luke, maybe it's time for a proper alien companion. Maybe another species, but even a human from another planet would be cool.