Wide topic! IMHO:
1. Complexity and special requirements (security, specific treatment,...) of the business rules the database is supposed to modelize.
2. Complexity of the database schema (tables structures, relationships, constraints...).
3. Deviation from the standard behaviour of the "typical Access model", use of dynamic queries, complex VBA functions, access to external data or data providers (external files, RDBMS Servers), communication and/or interactivity with external processes (Excel, Outlook, Word, etc.) or the O.S. (Active Directory, local or remote COM servers, etc.)
4. (unfortunately) poor (or lack of) respect of the normal forms (database normalization).