When I upgraded from 3.1.4 to 3.3 I started getting a memory error whenever WPMU Plugin Stats ran the regenerate. It might also just be coincidental with the number of sites + plugins we added since last I ran the plugin.
Full details about how I fixed it to run here:
Might be some additional optimizations that could happen. Although this will probably be a potential problem for any large multisite network with a lot of plugins.