See http://www.telerik.com/community/forums/aspnet-ajax/tooltip/changing-targetcontrol-on-the-client.aspx
It should be expected that this timeout around the public API is not needed and the problem is taken care of internally by the control.

When the page is in RTL mode and the manual close button of the RadToolTip is hovered it changes its position slightly.

The main wrapper of the tooltip is animated and the callout is positioned and shown after that. This makes it "pop" after the animation finishes. Disabling the shadow (EnableShadow=false) mitigates the effect somewhat.
The callout can be positioned initially (if ShowCallout is not set to false) where it should be according to the Position property of the RadToolTip and its location can be updated at the end of the entire showing process again (as it is now).

When Tooltip ContentScrolling property is set to Auto the the tooltip dimensions are not computed properly and the layout looks inconsistent (i.e. usually the left and/or right borders are missing).

Possible workarounds are:

1) using content that will fit in the tooltip and leaving the ContentScrolling property to its default value

OR

2) using some JavaScript to modify the dimensions:
function OnClientResponseEnd()
{
	var activeTooltip = Telerik.Web.UI.RadToolTip.getCurrent();
	if (activeTooltip)
	{
		var contentElement = activeTooltip.get_contentElement();
		if (contentElement)
		{
			contentElement.style.width = parseInt(contentElement.style.width) - 15 + "px";
			contentElement.style.height = parseInt(contentElement.style.height) - 15 + "px";
			contentElement.style.overflow = "auto";
		}
	}
}

where this is attached to the OnClientResponseEnd event of the RadToolTipManager.

The ContentScrolling property does not take effect under IE10. The end result is that the control behaves as if the property has its Default value (i.e. the browser will handle the overflow of the elements, which means large content will stretch the tooltips).

Many controls have items tooltip (RadComboBox, RadListBox, etc...) and every time is a pain to bind data in.

You could implement support to "DataToolTipField" .....

When we have templates the generation of the clientIDs is dynamical. If some controls are removed and added back to the controls collection their clientIDs are changed. We can give a reference to the control in the Add method and onprerender the ToolTipManager could find their ClientIDs.
 E.g. the following demo: http://demos.telerik.com/aspnet-ajax/orgchart/examples/applicationscenarios/integrationwithradtooltip/defaultcs.aspx. is not working when we have DrillDown.

When creating tooltips dynamically it is possible that on a given condition some of them should not be shown anymore. A reference to them can be obtained through the manager (getToolTipByElement(HTMLelement)  method), but they cannot be removed. Calling dispose() removes the handlers, but the JavaScript object remanis, so re-adding a tooltip for the same element is not easily possible. There should be a method like removeToolTipByElement(HTMLelement) or removeToolTip(RadToolTipInstance) that will also remove the JavaScript object, popup element, etc.