If your Smart Lists are processing slowly, you may be able to speed them up using Segmentations for exclusion lists.
Many companies maintain email exclusion lists based on a number of criteria. In Marketo, these are often set up using Smart Lists that are then referenced in "Member of Smart List" filters. However, Smart Lists that reference other Smart Lists can be slow to resolve. Using a Segmentation for your exclusion lists instead of Smart Lists can help your campaigns and programs run more efficiently.
Instructions for setting up Segmentations can be found here: http://docs.marketo.com/display/public/DOCS/Create+a+Segmentation.
You can then use the Segmentation filters in your Smart List rather than the "Member of Smart List" filters: http://docs.marketo.com/display/public/DOCS/Use+Segment+Filters+in+a+Smart+List.