Space Hulk: Death Angel - playing a 'multi-player' game solo
I find it harder with more players. Mostly because people tend to coordinate less... and so suboptimal decisions are more common.

There also is the issue of more genestealers per event card, but more troops means more shots made. 

Worst blowouts I've seen have been 6p games.

I've run the game with a 3p setup for 2p, with one of the two controlling two groups, and it works fine that way. (P3 dropped out after turn 1.)