Could you examine the network tab of the browser dev toolbar and see what is the timing of the request? The goal is to see whether the request is initiated immediately and it takes a while to travel to the server, or it takes time to initiate the request.
If it is the former, then the issue is most likely related to the network and/or server performance/load and there is nothing we could do about it. If it is the latter, you could try simplifying the page to improve its performance. For example, rarely used functionality can be put into RadWindows so their iframes will only be loaded on demand, validation will have less fields to work with and the POST request will have less fields.
Another thing that may help reduce the server load and the resources a client machine requests from your server is using the CDNs we provide (for both skins and scripts), in addition to the MS AJAX CDN. There is even a simple web.config switch that will result in a combined script/stylesheet being downloaded to the client, instead of having many requests. You can find it here (see the Telerik.ScriptManager.TelerikCdn.CombinedResource and Telerik.StyleSheetManager.TelerikCdn.CombinedResource keys).
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