I have a CTD from time to time when entering an area (through a door). It is not strictly repeatable as the only common condition seems to be certain amount of time spent playing as usual. I kind of suspect it may have something to do with memory and buffering. I use Streamline, but no Streampurge setting combination solves the issue. I have changed iPreloadSizeLimit to 6 times larger to accommodate for my FCOM+QTP3 etc. mod-heavy load list, but it doesn't seem to help either. I strongly suspect the problem lies not with a particular mod but with the way Oblivion handles them all (i.e., a memory/buffer/cache issue). Any ideas?

Yes, I have the same overload issue, which is not so strange in my case as I run so many mods on my ageing rig. It's the same with Morrowind/Oblivion/Fallout 3 - so my guess is that it's connected to how the Gamebryo engine handles things. It basically bogs down after a while - and a common issue is CTD's when entering/exiting an interior. One thing you should do is disabling autosave on wait/rest/travel. Also, try to reduce the spawn rate somewhat if you can - I'm using the Slightly Reduced one with FCOM.

Can spawning really affect the game when playing mostly inside the Imperial City?

The amount of spawns are probably the most important factor when it comes to performance, but FCOM doesn't affect the amount of NPCs in Imp City so nope. Unless you're using mods that add NPCs to Imp City, of course. Then, yes.

Besides turning off autosaves, make sure you have no interfering background processes running, either by running the game on a clean boot or using Game Booster or a similar utility. It will also free up some memory.