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I see this mentioned in a story covering US interventions in foreign elections:

In his memoir, the former Defense Secretary Robert Gates accuses Richard Holbrooke, the Obama administration’s special representative for Afghanistan and Pakistan, of “doing his best to bring about the defeat of [Hamid] Karzai” in the Afghan elections of 2009.

What would be the motivation for the US (or at least for Holbrooke, if he somehow acted on his own initiative) to (allegedly) mount such a campaign against Karzai?

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After 2001 when Taliban Government fell then there was a question of who (and more importantly how) will rule the Afghanistan? So, there was a conference in Bonn,Germany. Hamid Karzai was appointed the chairman of interim administration. Later he won the election of 2004.

However, Hamid Karzai had some contention with the USA. He always wanted USA to take harder actions against Pakistan. In his viewpoint Pakistan was nurturing terrorists. Yet George W. Bush made Pakistan a 'major non-NATO ally'. Karzai said in an interview,

They have blamed Pakistan in the past as well for nurturing sanctuaries — Obama did, Hillary Clinton did, their defense secretaries did. They blamed Pakistan but kept bombing Afghanistan

Another point of discontentment was USA (and coalition) didn't care about Afghan lives. In his viewpoint,

This is an unending war where we die. We Afghans are being used as cannon fodder, as ammunition. ... They would say that they want to fight the Soviet Union to the last Afghan. They want to pursue their interests at the cost of every last Afghan. We don’t want to become the battleground for the U.S.’s objectives in this region, but that is what it is going towards.

Another U.S General McChrystal said about Karzai,

It was the civilian casualties that drove him crazy. He(Karzai) was convinced that it would cause us to lose. “You’re creating so much hate and ill will that we will lose the war,” he told McChrystal.

One other point of discontent was the corruption. In his viewpoint the corruption coming through the international donor contract was much significant. In another interview he said,

I knew that yes, we had corruption in the Afghan government system, in the delivery of services. But that was, in comparison to the corruption coming through the international donor contracts, and the way the money was spent, really insignificant.

There is also some other points. Hamid Karzai is seen inadequately capable to build democratic institutions. He had little experience in politics. One paper noted,

Karzai brought with him to office little experience in governing but many political habits derived from years of Afghan tribal and war politics, particularly power balancing rather than institution building and extreme suspicion about the other side’s motives when he felt threatened.

Maybe USA(or Holbrooke) wanted someone else who are more malleable to their policy. This can be the motivation to replace him.

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    He was correct about Pakistan harboring terrorists; the man Afghanistan was torn apart to find, Osama Bin Laden, was eventually found and assassinated in Pakistan. And there were problems through the Afghan war with fighters crossing the border and hiding in Pakistan. – pjc50 Dec 2 at 9:05
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    tl;dr He criticized U.S.A's warmongering and tried to stand for his people. U.S.A. doesn't forgive that. – Tomáš Zato - Reinstate Monica Dec 2 at 14:59
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    @TomášZato-ReinstateMonica - Could be, or perhaps Karzai was installed to be a malleable puppet to the Bush administration, and the Obama administration, having different goals in Afghanistan, was less inclined to look the other way and prop him up on issues such as corruption and abuses by regional warlords because Karzai wasn't "their guy." – PoloHoleSet Dec 2 at 16:31

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