Yes to heavily modded. Some profiles more than others, but I don't think I have any that have under 90 active plugins. Yes to ILS issues - in some profiles. When I initially tried it out, I went back to a heavy profile that I had abandoned as unstable (part of the problem I am having with this in general is that those most likely to be excited about using this seem most likely to have a large and varied mod list) and tried out some of the places it would inevitably hang. Exteriors were common, but I had often used the Bannered Mare for testing it because of all the NPCs in town that went in, as well as Solitude Docks. I had another I couldn't get to Dawnstar in.
Because of Josh talking about his screenshot profile, I also loaded one that I was testing 'pretties' on, that was ...problematic but not as predictably so, and made the run along the main roads, saved in exteriors and reloaded, in and out of buildings etc. The one I just tried it on is a trimmed version of the first, a winter one for my nord that includes CoT Winter, Frostfall, W&C, the new Seasons of Skyrim Winter, Hunterborn, blah blah. This is the trimmed version, ha. I haven't messed with ugrids at all.
The profile with the most time played with this has gone to level 10 starting in the orc fortress, not as heavy - 100 active. That is light for me, which could be embarrassing, I guess. It has gotten one random CTD in the wilderness... I can't say if it is just one of those weird things, a script issue, cranky game, or a 'new' CTD. I know that going in and out of Markarth was much easier for me than the last go I gave it - but I do not have the last one to load up. So... the one that has the most time on it may not be the best example, because it was cleaner and trimmer than the others, and so less prone to issues. The ones that had issues that WERE resolved by this, I haven't gone back to seriously play on because I feel they were inherently unstable regardless.
I started all this game modding over to go with an SR semi-legendary + extras, but am kind of thinking I need to suck it up and do a full STEP profile if only for easier comparisons in testing.