The following changes in VS 2015 will affect your development if you upgrade from VS 2012/2013,
IIS 7/8 Express is uninstalled, and IIS 10 Express is installed. VS2015 uses
<solution folder>\.vs\config\applicationHost.config as IIS Express configuration file. This new configuration is based on IIS 10 Express, so not fully compatible with previous IIS Express releases. The changes break the following scenarios.
Settings Overridden in Web.Config Leads to 500.19 Errors
Many settings such as MIME types are significantly changed in IIS 10 Express (.vs\config\applicationHost.config). So if you added your own MIME types in web.config in the past, and now you might hit 500.19 reporting that duplicate elements are detected.
A workaround that works for all IIS Express releases is to always remove such elements from web.config and then add them.
This does not only apply to MIME types, but also other IIS settings if they vary from IIS 7/8 Express to IIS 10 Express.
Changes to Global Configuration File Does Not Take Effect
Of course, you will have to modify .vs\config\applicationHost.config from now on, unless you do want to enable the global configuration file via project file hack.