I recently noticed an odd issue that pops up sporadically.

When I exit from an interior to an exterior (but never the other way), there is a chance of the game hanging at the loading screen. The loading screen is either blank, or shows one of the loading screen tips, but it hangs there forever and the transition never happens.

At this point, the game can only be killed via Task Manager.

When this happens, a valid auto-save is usually generated, which can be loaded. If I load the autosave and re-attempt the transition, it always works.

One of the spots where it happens quite a bit is Solitude, exiting from the Temple of the Divines. It doesn't happen every time, but for sure once per session if I visit the Temple. The only mods that affect Solitude that I have installed are SIMM (but it affects pretty much every static object everywhere) and a Solitude retexture pack.

It can also happen in other places where transition from an Interior-type cell to an Exterior-type cell is involved (i.e. exiting from a cave into Skyrim, or exiting from a building into a city). It usually happens after 30 minutes or more of gameplay time - almost never early in the game, but after I'm over 30 min/1 hour mark, it's likely to happen at least once.

I do not have savegame bloat. I suffer from occasional CTDs while traveling in the wilderness, but they are sporadic and not too common.

I am running 210 mods, but most of them are either texture packs or craftable armors. The heaviest gameplay-related mods I have are Deadly Dragons, More Hotkeys Please and Vilja.

I heard about cleaning update.esm with TES5EDIT, would it possibly help? And is it wise to mess with an official Bethesda file?

How long have you waited for the loading screen on the interior exterior loads? I noticed after Hearthfire that sometimes it would take several minutes to load the cell. The Unofficial Patches seemed to have fixed this as I don't notice any more.