I haven't had any major issues with RU4, RU5, or RU6. I do hate having to redo the OWA customizations every time. (logon.aspx, logoff.aspx, startpage.aspx, basicmessageview.aspx, basicreadmessage.aspx, and basicautosaveinfo.aspx - most people probably don't have this many customizations)
The "Create native images for .net assemblies" hasn't taken too long for me. Going from RU5 to RU6 (not sure if that makes a difference as opposed to going from SP1 RTM or an earlier RU) I think it took less than 4 minutes per server. I seem to remember one of the previous rollups may have taken 10-15 minutes at that step.
Our Exchange servers: Quad Core Xeon 3GHz (2 processors), 16GB RAM, 10K directly attached SAS storage, Windows Server 2008, Groupshield 7.0.1 (with HF447121). 4 servers: 2 client access/hub transport and 2 mailbox/hub transport. About 1400 total mailboxes.
No new persistent errors as of the morning after applying RU6.
We have finally been stable as of Exchange 2007 SP1 RU5 along with Groupshield 7.0.1 with HF447121. Before that combination things were not going well. (I think mainly due to Mcafee Groupshield 7.0 running with Exchange Server 2007 SP1 and most importantly, Windows Server 2008 - but Mcafee finally got on the ball and fixed the issues with server 2008)
I hope your rollups go as smoothly as mine.